RESUMO
Aims: The aim of this study is to investigate the effects of islet cells and mesenchymal stem cells transferred together in the amniotic membrane (AM) in order to preserve the viability and functionality of islet cells on the success of islet transplantation in diabetes mellitus-induced rats. Methods: A total of 80 male Wistar albino rats, aged 3.5-4 months, were included in this study. While 40 Wistar Albino rats were used for the process of islet cell isolation, 40 Wistar Albino rats were used to establish experimental groups. These rats were assigned to five experimental groups including eight rats in each. These groups were AM, amniotic membrane + mesenchymal stem cell (AM + MSC), amniotic membrane + islet cell (AM + IC), amniotic membrane + islet cell + mesenchymal stem cell (AM + IC + MSC), and sham groups. The study was concluded for 28 days. Results: Although there was no significant difference between AM + IC and AM + IC + MSC groups in terms of mean blood glucose levels, both groups had statistically different values compared to the sham group. A significant difference was observed between the AM + IC and AM + IC + MSC groups in the c-peptide levels before and after transplantation. Immunohistochemical staining illustrated the presence of insulin-positive cells in both AM + IC and AM + IC + MSC groups. Moreover, BrDU (+) cells were determined in AM + IC and AM + IC + MSC groups using BrDU staining. Conclusion: The study results indicated that transplanting islet cells into the omentum by being packaged in AM preserved their viability and function, leading to significant effects on blood glucose and c-peptide levels.
Assuntos
Âmnio , Diabetes Mellitus Experimental , Transplante das Ilhotas Pancreáticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Transplante das Ilhotas Pancreáticas/métodos , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Âmnio/citologia , Âmnio/metabolismo , Ratos Wistar , Masculino , Ratos , Glicemia/metabolismo , Peptídeo C/sangue , Ilhotas Pancreáticas , Insulina/metabolismoRESUMO
Background: Pelemir (Cephalaria syriaca) is a bitter-tasting ancestral legume with a high polyphenol content and emerging potential as a functional food ingredient. This study investigated the acute metabolic effects of pelemir-enriched bread in adults. Methods: In this two-phase non-randomized trial, 60 participants in three groups (n = 20 per group: healthy controls [HCs], individuals with obesity [OB], and individuals with type 2 diabetes [T2D]) consumed regular or pelemir-enriched bread on two separate test days. Postprandial glucose, insulin, C-peptide, GLP-1, PYY, ghrelin, leptin, triglyceride, and IL-6 were measured over 120 min. Subjective appetite ratings were evaluated using visual analog scales (VASs). The incremental area under the curve (iAUC) values were compared using Wilcoxon tests and linear mixed-effects models. Results: Pelemir-enriched bread significantly increased iAUCs for insulin (p = 0.014), C-peptide (p = 0.046), and GLP-1 (p = 0.039) compared to regular bread. There was no significant change in iAUC for glucose. Group-stratified analyses showed a higher postprandial iAUC of glucose, insulin, and C-peptide in the OB group compared to the HC group. VAS-based appetite ratings did not show significant changes in hunger, fullness, or desire to eat, but a borderline significant reduction was observed in prospective food consumption after pelemir-enriched bread (p = 0.050). Conclusions: Acute consumption of pelemir-enriched bread may modulate postprandial insulin and incretin responses. Its modest impact on subjective appetite regulation supports further investigation of pelemir as a functional food rich in polyphenols, especially in populations with metabolic dysfunction.
Assuntos
Pão , Caprifoliaceae , Diabetes Mellitus Tipo 2 , Obesidade , Extratos Vegetais , Período Pós-Prandial , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos de Casos e Controles , Obesidade/sangue , Obesidade/dietoterapia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/dietoterapia , Peso Corporal Ideal/fisiologia , Período Pós-Prandial/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Caprifoliaceae/química , Extratos Vegetais/farmacologia , Pão/análise , Alimentos Fortificados/análise , Apetite/efeitos dos fármacos , Estatísticas não Paramétricas , Modelos Lineares , Insulina/sangue , Peptídeo C/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Escala Visual Analógica , Ingestão de Alimentos/efeitos dos fármacos , Incretinas/sangue , Polifenóis/farmacologiaRESUMO
OBJECTIVE: The 72â h fasting test, gold standard for diagnosing endogenous hyperinsulinemic hypoglycemia (EHH), is cumbersome and costly. We evaluated exenatide, a GLP-1 receptor agonist, as a faster, less burdensome alternative diagnostic tool. DESIGN AND METHODS: In this prospective, placebo-controlled, double-blind, randomized cross-over, proof-of-principle study, 10â µg intravenous exenatide was compared to placebo in 14 patients with confirmed EHH in a fasting test. Fourteen matched controls received 10â µg exenatide unblinded. Clinical monitoring and measurements of glucose, insulin, C-peptide, and proinsulin were performed for 4â h. Follow-up for EHH patients included imaging and histology. RESULTS: Exenatide induced diagnostic hypoglycemia in 6 of 14 EHH patients (42%) compared to none with placebo (P = .005). In patients with EHH, glucose nadir occurred earlier after exenatide (67â¯min [95% CI 50-142] vs 210â¯min [95% CI 174-219], P < .0001) and at lower glucose levels (2.68â¯mmol/L [95% CI 2.26-3.02] vs 3.2â¯mmol/L [95% CI 2.92-3.77], P < .0001) compared to placebo. Proinsulin levels 120â min post-exenatide were higher in patients with EHH [69â¯pmol/L (95% CI 3.8-232)] compared to controls [9â¯pmol/L (95% CI 4.5-16.9), P = .0001]. Compared to the fasting test, exenatide significantly shortened time to hypoglycemia (1.38â h [95% CI .67-2.99] vs 12â h [95% CI 1.44-36.1], P = .032). Exenatide was well tolerated and preferred by patients over the fasting test. CONCLUSIONS: Exenatide is a promising, faster, less cumbersome, and less expensive diagnostic tool for EHH compared to the fasting test. Larger trials are warranted to confirm its diagnostic utility. Trial Registration ClinicalTrials.gov (NCT04909333).
Assuntos
Exenatida , Hiperinsulinismo , Hipoglicemia , Hipoglicemiantes , Peptídeos , Humanos , Método Duplo-Cego , Estudos Cross-Over , Feminino , Masculino , Pessoa de Meia-Idade , Hipoglicemia/diagnóstico , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Glicemia/análise , Glicemia/metabolismo , Adulto , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/sangue , Idoso , Estudos Prospectivos , Proinsulina/sangue , Insulina/sangue , Estudo de Prova de Conceito , Peptídeo C/sangueRESUMO
AIMS: These participant-level exploratory analyses evaluated the effects of orforglipron, a once-daily, orally administered non-peptide glucagon-like peptide-1 receptor agonist, versus dulaglutide and placebo, on ß-cell function and insulin sensitivity biomarkers. MATERIALS AND METHODS: Participants (N = 378) in this 26-week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45 mg), dulaglutide (1.5 mg), or placebo. Treatment effects on ß-cell function and insulin sensitivity markers were assessed, including homeostatic model assessment indices of ß-cell function and insulin resistance (HOMA-B and HOMA-IR, respectively); fasting C-peptide, insulin, serum glucose, and glucagon; adiponectin; insulin-like growth factor binding protein 2; proinsulin; and the proinsulin/insulin ratio. RESULTS: Orforglipron doses of 12 mg and higher were associated with improved ß-cell function and insulin sensitivity. HOMA-B increased up to 123% (C-peptide) and 132% (insulin) with orforglipron doses of 12 mg and higher from baseline to week 4 before stabilising. HOMA-B increases were greater with all orforglipron doses than with dulaglutide. Additional ß-cell function biomarkers, such as fasting proinsulin and the proinsulin/insulin ratio, also improved with orforglipron doses of 12 mg and higher compared with baseline and to a greater extent than seen with dulaglutide. HOMA-IR values decreased up to 16% (C-peptide) and 23% (insulin) with orforglipron by week 26. Reductions in HOMA-IR (insulin) were significant versus baseline only for the highest dose. IGFBP-2 and adiponectin, corollary biomarkers of insulin sensitivity, were generally improved with orforglipron. CONCLUSIONS: Increased HOMA-B and improved metabolic biomarkers suggest that treatment with the orally administered non-peptide GLP-1 receptor agonist orforglipron enhanced pancreatic ß-cell function and insulin sensitivity in patients with T2D.
Assuntos
Diabetes Mellitus Tipo 2 , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Hipoglicemiantes , Resistência à Insulina , Células Secretoras de Insulina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Biomarcadores/sangue , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Peptídeo C/sangue , Administração Oral , Idoso , Insulina/sangue , Método Duplo-Cego , Adiponectina/sangue , Adulto , Oxidiazóis , Compostos de FlúorRESUMO
Introduction: Maintaining endogenous insulin secretion in type 1 diabetes (T1D) long after its onset, and thus the need for early diagnosis and searching for factors preserving the secretory function of ß-cells, has become an important goal of current research. The aim of the study was to evaluate C-peptide secretion in T1D children with at least 1 year disease duration and to investigate the potential role of body mass index (BMI) and betatrophin on residual ß-cell function. We also assessed factors that may affect betatrophin levels. Methods: 121 children and adolescents suffering from T1D were divided into groups based on: clinical significance of C-peptide; BMI-SDS <1 and ≥1; and disease duration to compare C-peptide and betatrophin levels and determine the importance of these changes. Results: Of the children recruited, 44 (36.36%) had clinically significant C-peptide (> 0.23 ng/ml), and compared with the group with clinically insignificant C-peptide they had later onset (P<.001), shorter duration of illness (P<.001), lower daily insulin requirement (P=.025), lower mean HbA1c over the past year (P=.002), higher betatrophin levels (P=.019), and BMI-SDS at diagnosis (P=.013). Betatrophin levels correlated positively with C-peptide (P=.043) while negatively with patient's age (P<.001), BMI-SDS (P=.010), disease duration (P=.006), HbA1c level at sampling (P=.022), average HbA1c level over the past year (P=.006), and basal insulin (P=.001). Conclusion: The positive significant relationship between betatrophin and C-peptide concentrations may indicate betatrophin as a potential biomarker of long-lasting residual ß-cell function. Negative correlation with BMI identifies the ongoing need to maintain an appropriate body mass.
Assuntos
Proteínas Semelhantes a Angiopoietina , Peptídeo C , Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Hormônios Peptídicos , Humanos , Peptídeo C/sangue , Peptídeo C/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Criança , Proteína 8 Semelhante a Angiopoietina , Masculino , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiologia , Feminino , Adolescente , Hormônios Peptídicos/sangue , Proteínas Semelhantes a Angiopoietina/sangue , Índice de Massa Corporal , Insulina/metabolismo , Biomarcadores/sangue , Indução de Remissão , Pré-EscolarRESUMO
OBJECTIVES: To describe the prevalence of cardiovascular disease (CVD) at the time of diagnosis of adult-onset type 1 (T1D) and type 2 (T2D) diabetes, in a recent cohort and compare to a previous cohort from the same region. Further, to explore factors influencing the prevalence of pre-existing CVD, including age, sex, body mass index (BMI) and C-peptide; in the later cohort also heart failure, hyperlipidaemia, tobacco use and physical activity. DESIGN: Two prospective cross-sectional cohort studies compared. SETTING: All primary health care centres and hospitals in Kalmar and Kronoberg counties in Southeastern Sweden. PARTICIPANTS: Adults with newly diagnosed T1D or T2D (classified by combination of islet antibodies and C-peptide) in 1998-2001 and 2016-2017. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of hypertension and CVD at diagnosis of diabetes, and associations with beta-cell function, in two cohorts collected 15 years apart. Further, to explore factors influencing the prevalence of hypertension and CVD, and level of C-peptide. RESULTS: In patients with newly diagnosed T2D, mean age-at-onset had decreased (66±14.1 years vs 63±12.6, p≤0.001) and mean BMI had increased (29.0±5.4 vs 31.4±5.8 kg/m2, p≤0.001). Prevalence of pre-existing myocardial infarction had decreased in both T1D (18% vs 7%, p=0.03) and T2D (25% vs 11%, p≤0.001). Pre-existing hypertension had increased in both T1D (23% vs 40%, p=0.01) and T2D (44% vs 61%, p≤0.001). C-peptide level was lower and was associated with several cardiovascular conditions in newly diagnosed T2D in 2016-2017 (p=0.048 p≤0.001). CONCLUSIONS: Patients with newly diagnosed T2D were younger, with higher BMI, compared with 15 years earlier, a challenge for diabetes care. Prevalence of pre-existing myocardial infarction had decreased notably, in line with, but still less than in the general population; while pre-existing hypertension had increased, in both diabetes types. C-peptide was associated with several cardiovascular conditions in newly diagnosed T2D in the recent cohort, which warrants further investigation.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Humanos , Suécia/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Doenças Cardiovasculares/epidemiologia , Células Secretoras de Insulina/fisiologia , Estudos Prospectivos , Idoso , Prevalência , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Índice de Massa Corporal , Peptídeo C/sangue , Idade de Início , Hipertensão/epidemiologia , Adulto , Fatores de RiscoRESUMO
Type 2 Diabetes Mellitus (T2DM) remains a significant global health challenge, necessitating more effective therapeutic strategies. This study was to observe the impact of semaglutide on the C-Peptide levels and glycemic variability. This retrospective evaluation was conducted from January 2020 to January 2023 at our hospital, involving 172 patients diagnosed with T2DM. Patients were stratified into two groups: the observation group (86 patients) received semaglutide injections plus metformin, and the control group (86 patients) received only metformin. Treatment efficacy was assessed using changes in HbA1c, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h BG), and C-Peptide levels. Additional evaluations included changes in glycemic variability indicators such as standard deviation of blood glucose (SDBG), mean of daily differences (MODD), and mean amplitude of glycemic excursions (MAGE). The observation group showed significantly greater improvements in glycemic control and C-Peptide levels compared to the control group. Specifically, the observation group achieved a significant reduction in HbA1c from 70 mmol/mol to 53 mmol/mol, FBG from 10.91 mmol/l to 6.12 mmol/l, and increased C-Peptide levels in both fasting and postprandial states. Improvements in glycemic variability were also more pronounced in the observation group. There was no significant difference in the incidence of adverse events between the two groups. Semaglutide combined with metformin significantly enhances the efficacy of treatment in T2DM patients, with marked improvements in C-Peptide levels, glycemic control, and reduction in glycemic variability. This combination therapy not only offers superior glucose management but also appears to bolster pancreatic function.
Assuntos
Peptídeo C , Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Peptídeo C/sangue , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Estudos Retrospectivos , Glicemia/análise , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Idoso , Metformina/uso terapêutico , Metformina/administração & dosagem , Resultado do Tratamento , Peptídeo 1 Semelhante ao GlucagonRESUMO
The study evaluated the effect of semaglutide treatment for type 2 diabetes mellitus (T2DM), specifically examining its effect on C-peptide levels. A total of 80 patients hospitalized for T2DM were included (January 2022-December 2023), and all patients had conventional treatment with oral metformin. Patients in the control group received subcutaneous insulin aspart, while patients in the observation group received subcutaneous semaglutide. Key variables, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2h-PBG), and time to target blood glucose, were assessed at the baseline and again after three months. Serum endothelin-1 (ET-1), functional vasodilation (FMD), fasting C-peptide, fasting insulin (FINS), and the insulin resistance index (Homa-IR) were also measured. At the end of three months, the observation group had significantly lower 2h-PBG (9.01±0.53 mmol/L) and FBG (6.13±0.68 mmol/L) than the control group (P<0.05). Additionally, the time to target glucose was shorter in the observation group (3.88±0.69 vs. 5.73±1.01 days, P<0.05). The observation group also had lower ET-1, higher FMD, and increased Homa-IR (P<0.05). In conclusion, semaglutide optimizes glycemic control, lowers insulin resistance, and increases vasorelaxation function. Semaglutide has great potential as a therapeutic agent in T2DM.
Assuntos
Peptídeo C , Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/farmacologia , Masculino , Feminino , Pessoa de Meia-Idade , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Hipoglicemiantes/uso terapêutico , Peptídeo C/sangue , Resistência à Insulina , Idoso , Endotelina-1/sangue , Insulina/sangue , Vasodilatação/efeitos dos fármacos , Metformina/uso terapêutico , Resultado do Tratamento , Peptídeo 1 Semelhante ao GlucagonRESUMO
BACKGROUND: Zimislecel is an allogeneic stem cell-derived islet-cell therapy. Data on the safety and efficacy of zimislecel in persons with type 1 diabetes are needed. METHODS: We conducted a phase 1-2 study of zimislecel in persons with type 1 diabetes. In part A, participants received a half dose of zimislecel (0.4 × 109 cells) as a single infusion into the portal vein, with an option for a second half dose within 2 years. In parts B and C, participants received a full dose of zimislecel (0.8 × 109 cells) as a single infusion. All the participants also received glucocorticoid-free immunosuppressive therapy. The primary end point in part A was safety. The primary end point in part C was freedom from severe hypoglycemic events during days 90 through 365, with a glycated hemoglobin level of less than 7% or a decrease of at least 1 percentage point from baseline in the glycated hemoglobin level at one or more time points between days 180 and 365. Secondary end points in part C included safety and insulin independence between days 180 and 365. Assessment of the primary and secondary end points in part C involved the participants who received the full dose of zimislecel as a single infusion in part B or C. Detection of serum C-peptide during a 4-hour mixed-meal tolerance test was used to assess engraftment and islet function. All the analyses were interim and not prespecified. RESULTS: A total of 14 participants (2 in part A and 12 in parts B and C) completed at least 12 months of follow-up and were included in the analyses. C-peptide was undetectable at baseline in all 14 participants. After zimislecel infusion, all the participants had engraftment and islet function, as evidenced by the detection of C-peptide. Neutropenia was the most common serious adverse event, occurring in 3 participants. Two deaths occurred - one caused by cryptococcal meningitis and one by severe dementia with agitation owing to the progression of preexisting neurocognitive impairment. All 12 participants in parts B and C were free of severe hypoglycemic events and had a glycated hemoglobin level of less than 7%; these participants spent more than 70% of the time in the target glucose range (70 to 180 mg per deciliter). Ten of the 12 participants (83%) had insulin independence and were not using exogenous insulin at day 365. CONCLUSIONS: The results of this small, short-term study involving persons with type 1 diabetes support the hypothesis that zimislecel can restore physiologic islet function, warranting further clinical investigation. (Funded by Vertex Pharmaceuticals; VX-880-101 FORWARD ClinicalTrials.gov number, NCT04786262.).
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Glicemia/análise , Peptídeo C/sangue , Diferenciação Celular , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/cirurgia , Seguimentos , Hemoglobinas Glicadas/análise , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Hipoglicemiantes/uso terapêutico , Imunossupressores/administração & dosagem , Infusões Intravenosas , Insulina/uso terapêutico , Ilhotas Pancreáticas/citologia , Transplante das Ilhotas Pancreáticas/efeitos adversos , Transplante das Ilhotas Pancreáticas/métodos , Transplante HomólogoRESUMO
AIMS: Bariatric surgery is a widely adopted intervention for managing obesity and improving glycaemic control in patients with type 2 diabetes mellitus (T2DM). This meta-analysis evaluates the impact of bariatric surgery on glycaemic and metabolic outcomes, including fasting blood glucose (FBG), postprandial glucose (PPG), HbA1c, C-peptide, HOMA-IR and fasting insulin levels. MATERIALS AND METHODS: Comprehensive search of PubMed, Scopus, EMBASE and Web of Science was conducted from inception to March 2025. Eligible studies were pooled using a random-effects model to calculate weighted mean differences (WMD) or standardized mean differences (SMD) with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics, and publication bias was evaluated using funnel plots and Egger's tests. RESULTS: Thirty-nine studies with 3855 participants were included. Bariatric surgery resulted in significant reductions in FBG (WMD = 3.461; 95% CI: 2.740-4.182, p < 0.001), PPG (WMD = 6.153; 95% CI: 4.298-8.007, p < 0.001) and HbA1c levels (WMD = 2.085; 95% CI: 1.561-2.608, p < 0.001). Modest but non-significant improvements were observed in C-peptide (SMD = 0.358; 95% CI: -0.043 to 0.759, p = 0.075) and fasting insulin (SMD = 1.593; 95% CI: -0.392 to 3.577, p = 0.104). Significant reductions in HOMA-IR levels (WMD = 2.480; 95% CI: 1.010-3.950, p = 0.009) were noted. High heterogeneity was observed across most outcomes. Publication bias was detected for FBG and HbA1C, while it was undetected for the rest of the outcomes. CONCLUSIONS: Bariatric surgery significantly improves glycaemic and metabolic outcomes in obese patients with T2DM. These findings support its integration into diabetes management pathways, offering a promising approach for long-term disease control and complication reduction. Further research is needed to evaluate long-term outcomes and mechanisms.
Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Obesidade , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/cirurgia , Obesidade/complicações , Obesidade/metabolismo , Obesidade/sangue , Glicemia/análise , Glicemia/metabolismo , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Resultado do Tratamento , Resistência à Insulina , Peptídeo C/sangue , Insulina/sangue , Controle Glicêmico , Feminino , Jejum/sangueRESUMO
Gastrointestinal hormones are essential for nutrient handling and regulation of glucose metabolism and may affect postprandial blood redistribution. In a randomized cross-over design in 10 healthy men, the involvement of glucose-dependent insulinotropic polypeptide (GIP) in splanchnic blood flow regulation was investigated using an infusion of GIP receptor antagonist (GIPR-An) GIP(3-30)NH2 during ingestion of oral glucose (75 g). In five separate sessions, we investigated GIP(1-42), GIPR-An with and without oral glucose, oral glucose alone, and a control saline infusion. Blood flow was assessed by phase contrast MRI, hepatic oxygen consumption by T2*, and plasma glucose, insulin, C-peptide, glucagon, GIP, GIPR-An, glucagon-like peptide 2, and bone metabolism markers by frequent blood sampling during all sessions. We found GIP(1-42) to stimulate blood flow in the superior mesenteric artery by â¼10% in the fasting state. Oral glucose alone increased mean blood flow in the superior mesenteric artery by â¼70% and portal vein by â¼40% of baseline. During oral glucose ingestion with concurrent infusion of GIPR-An, blood flow in the superior mesenteric artery was â¼22% lower. The hormone infusions did not affect blood flow in the hepatic artery and the celiac artery. Infusion of GIPR-An during oral glucose ingestion resulted in lower insulin secretion and higher levels of carboxy-terminal collagen crosslinks (bone resorption biomarker) compared with saline infusion, whereas glucagon levels were unaffected by both the injection of GIP and the GIPR-An infusions. We conclude that endogenous GIP increases splanchnic blood flow and contributes to postprandial intestinal hyperemia in healthy men. ARTICLE HIGHLIGHTS: Administration of the gut hormone glucose-dependent insulinotropic polypeptide (GIP) increases splanchnic blood flow. We investigated the role of endogenous GIP in splanchnic blood flow regulation using a receptor antagonist in humans. Oral glucose ingestion increased blood flow in the superior mesenteric artery by â¼70%, and the increase was significantly lower during concurrent infusion of the GIP receptor antagonist. Thus, endogenous GIP contributed â¼22% of the postprandial increase in superior mesenteric artery blood flow. We have identified a novel physiological aspect of vascular biology related to the GIP receptor in humans. Treatments targeting the GIP receptors are likely to affect splanchnic blood flow.
Assuntos
Polipeptídeo Inibidor Gástrico , Período Pós-Prandial , Circulação Esplâncnica , Humanos , Polipeptídeo Inibidor Gástrico/farmacologia , Masculino , Período Pós-Prandial/fisiologia , Período Pós-Prandial/efeitos dos fármacos , Circulação Esplâncnica/efeitos dos fármacos , Circulação Esplâncnica/fisiologia , Adulto , Receptores dos Hormônios Gastrointestinais/antagonistas & inibidores , Insulina/sangue , Fragmentos de Peptídeos/farmacologia , Glicemia/metabolismo , Estudos Cross-Over , Glucagon/sangue , Adulto Jovem , Glucose/administração & dosagem , Glucose/farmacologia , Artéria Mesentérica Superior/efeitos dos fármacos , Peptídeo C/sangue , Peptídeo 2 Semelhante ao Glucagon/sangue , Veia Porta/efeitos dos fármacosRESUMO
Publications of systematic studies on analyte stability after repeated freezing and thawing of samples are rare. We examined the stability of 17 endocrine analytes in pooled serum and/or EDTA plasma after one to four cycles of repeated freezing at -80 °C and thawing. Pooled serum and plasma samples were used. Following baseline measurements in fresh samples (T0), four aliquots (T1-T4) were frozen at -80 °C, and subjected to one to four cycles of freezing and thawing before analysis on the same day. Results were compared to baseline measurements (T0) and to samples frozen once (T1), and were adjusted using quality control material to account for analytical variation between the two time points of analysis. Analytes were considered stable based on statistical significance and percent change compared to allowable bias (AB) based on biological variation. According to criteria based on AB, serum 17-OH progesterone, aldosterone, androstenedione, anti-müllerian hormone, cortisol, dehydroepiandrosterone sulphate, proinsulin C-peptide and sexual-hormone-binding-globulin, and plasma aldosterone and cortisol were stable for four cycles of freezing and thawing. Only serum free thyroxine was considered unstable. For serum erythropoietin, estradiol, free triiodothyronine, human chorionic gonadotropin, human growth hormone, insulin-like growth factor-1, prolactin and plasma free thyroxine, human growth hormone, parathyroid hormone results were not conclusive. Based on average results of pooled samples, eight out of 17 analytes appeared stable for four freeze-thaw cycles compared to AB, while free thyroxine in serum increased more than AB.
Assuntos
Congelamento , Hormônios , Humanos , Tiroxina/sangue , Hidrocortisona/sangue , Aldosterona/sangue , Prolactina/sangue , Sulfato de Desidroepiandrosterona/sangue , Androstenodiona/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Tri-Iodotironina/sangue , Hormônio Antimülleriano/sangue , Estradiol/sangue , Hormônio do Crescimento Humano/sangue , Criopreservação , Eritropoetina/sangue , Globulina de Ligação a Hormônio Sexual/análise , Globulina de Ligação a Hormônio Sexual/metabolismo , Gonadotropina Coriônica/sangue , Hormônios/sangue , Feminino , Peptídeo C/sangue , Plasma/químicaRESUMO
INTRODUCTION: Roux-en-Y gastric bypass (RYGB) increases the risk of postprandial hypoglycemia, whereas pregnancy decreases insulin sensitivity, which could be expected to counteract hypoglycemia. We examined if RYGB performed prior to pregnancy altered the postprandial glucose metabolism and enteropancreatic hormone responses to a mixed meal test (MMT). RESEARCH DESIGN AND METHODS: Twenty-three women with RYGB and 23 women matched on prepregnancy body mass index and parity underwent a 4-hour MMT in the first and third trimester of pregnancy with measurement of circulating levels of glucose, insulin, C-peptide, glucose-dependent insulin peptide (GIP), glucagon-like peptide 1 (GLP-1), glucagon, free fatty acids, and lactate. Biochemical hypoglycemia was defined as plasma glucose <3.5 mmol/L. RESULTS: Women with RYGB had earlier and higher peak glucose, lower nadir glucose levels, and a higher frequency of biochemical hypoglycemia compared with women without RYGB in both the first and third trimester. The lower glucose levels were preceded by markedly elevated total GLP-1 and insulin levels in women with RYGB, whereas total GIP levels were unaltered. The glucagon levels were lower in women with RYGB. In the first trimester MMT, peak and area under the curve of total plasma GLP-1 and serum insulin levels were negatively associated with nadir plasma glucose, while the early postmeal response of plasma glucagon was positively associated with nadir plasma glucose in the third trimester. CONCLUSIONS: These results provide novel insights into the combined effects of RYGB and pregnancy on postmeal glucose metabolism and enteropancreatic hormone responses during pregnancy, and how these changes associate with an increased risk of postprandial hypoglycemia. TRIAL REGISTRATION NUMBER: NCT03713060.
Assuntos
Biomarcadores , Glicemia , Derivação Gástrica , Hipoglicemia , Período Pós-Prandial , Complicações na Gravidez , Adulto , Feminino , Humanos , Gravidez , Biomarcadores/análise , Biomarcadores/sangue , Glicemia/análise , Glicemia/metabolismo , Peptídeo C/sangue , Seguimentos , Derivação Gástrica/efeitos adversos , Polipeptídeo Inibidor Gástrico/sangue , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Hipoglicemia/etiologia , Insulina/sangue , Estudos ProspectivosRESUMO
BACKGROUND: Higher concentration of insulin-like growth factor-1 (IGF-1) increases postmenopausal breast cancer risk, but evidence for insulin and c-peptide is limited. Furthermore, not all studies have accounted for potential confounding by biomarkers from other biological pathways, and not all were restricted to estrogen receptor (ER)-positive breast cancer. METHODS: This was a case-cohort study of 1,223 postmenopausal women (347 with ER-positive breast cancer) from the Melbourne Collaborative Cohort Study. We measured insulin, c-peptide, IGF-1, insulin-like growth factor binding protein-3, and biomarkers of inflammatory and sex-steroid hormone pathways. Poisson regression with a robust variance estimator was used to estimate risk ratios (RR) and 95% confidence intervals (95% CI) for ER-positive breast cancer per doubling plasma concentration and for quartiles, without and with adjustment for other, potentially confounding biomarkers. RESULTS: ER-positive breast cancer risk was not associated with doubling of insulin (RR = 0.97, 95% CI, 0.82-1.14) or c-peptide (RR = 1.01, 95% CI, 0.80-1.26). Risk seemed to decrease with doubling IGF-1 (RR = 0.80, 95% CI, 0.62-1.03) and insulin-like growth factor binding protein-3 (RR = 0.62, 95% CI, 0.41-0.90). RRs were not meaningfully different when exposures were modeled as quartiles. RRs were less than unity but imprecise after adjustment for inflammatory and sex-steroid hormone biomarkers. CONCLUSIONS: Circulating insulin, c-peptide, and IGF-1 were not positively associated with risk of ER-positive breast cancer in this case-cohort analysis of postmenopausal women. IMPACT: Associations between insulin and c-peptide and risk of ER-positive breast cancer in postmenopausal women are likely to be weak.
Assuntos
Neoplasias da Mama , Fator de Crescimento Insulin-Like I , Insulina , Pós-Menopausa , Receptores de Estrogênio , Humanos , Feminino , Neoplasias da Mama/sangue , Neoplasias da Mama/metabolismo , Neoplasias da Mama/epidemiologia , Pós-Menopausa/sangue , Receptores de Estrogênio/metabolismo , Pessoa de Meia-Idade , Fator de Crescimento Insulin-Like I/metabolismo , Insulina/sangue , Estudos de Casos e Controles , Idoso , Estudos de Coortes , Peptídeo C/sangue , Fatores de Risco , Biomarcadores Tumorais/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Peptídeos Semelhantes à InsulinaRESUMO
Background: Although immune checkpoint inhibitors (ICIs) are effective cancer drugs, ICI-induced diabetes is a rare but a life-threatening adverse event for patients. The deleterious action of ICI on pancreatic beta-cell function is a concern. However, the influence of ICI on insulin synthesis and secretion in patients with cancer without diabetes remains unknown. Methods: This study included 87 patients diagnosed with advanced cancer. Glucose metabolism markers (HbA1c, HOMA-IR) and indicators of insulin secretory capacity (HOMA-beta, C-peptide) were prospectively evaluated in patients with ICI-treated cancers to determine their association with cancer prognosis. Results: Patients with overall survival (OS) ≥ 7 months had substantially higher HOMA-beta levels at baseline (p=0.008) and 1 month after ICI administration (p=0.006) compared to those with OS <7 months. The median OS was significantly longer in patients with HOMA-beta ≥ 64.24 (13 months, 95%CI: 5.849-20.151, 37 events) than in those with HOMA-beta < 64.24 (5 months, 95%CI: 3.280-6.720, 50 events) (p=0.013). Further, the median progression-free survival (PFS) was significantly longer in patients with HOMA-beta ≥ 66.43 (4 months, 95%CI: 3.073-4.927, 33 events) than in those with HOMA-beta < 66.43 (2 months, 95%CI: 1.410-2.590, 54 events) (p=0.025). Additionally, multivariable logistic regression analysis revealed that a HOMA-beta value ≥ 64.24 independently predicted longer OS in ICI-treated patients. Conclusions: Pre-ICI HOMA-beta level is linked to longer OS in ICI-treated patients. This connection is significant and shows that insulin secretory capacity may predict ICI efficacy.
Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/metabolismo , Pessoa de Meia-Idade , Idoso , Prognóstico , Adulto , Estudos Prospectivos , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Insulina , Idoso de 80 Anos ou mais , Resistência à Insulina , Taxa de Sobrevida , Secreção de Insulina/efeitos dos fármacos , Peptídeo C/sangueRESUMO
PURPOSE: Geriatric diabetes is complicated by the frailty of this population, and hypoglycemia with insulin is not uncommon in these patients. Automated Insulin Delivery (AID) systems may provide better glycemic control in elderly patients with brittle type 2 diabetes. METHODS: Thirty-four patients (≥ 60 years) including cancer patients with brittle diabetes were switched to an AID system from multiple-dose insulin (MDI) treatment. HbA1c level, weight, total daily insulin requirement, and C-peptide, creatinine, and lipids were followed for at least six months. RESULTS: There were 34 patients (14 male, 41.2 %) with a median age of 67 (IQR 63.0-75.5). Six patients (17.6 %) were on chemotherapy and/or steroids (Ch/S). The patients' initial median HbA1c % was 9.3 (IQR 7.6-11.0), c-peptide level was 0.9 (IQR 0.5-2.2) ng/mL, and median total daily insulin dose was 41 IU (IQR 32-53). Six months after the patients were switched to an AID system their HbA1c % decreased to 7.1 (IQR 6.5-8.1), p < 0.001 and c-peptide increased to 1.21 (IQR 0.2-1.7) ng/mL, p = 0.878. Total insulin dose decreased with AID systems [32 IU (IQR 23.9-37.8)), p < 0.001]. There was a decrease in median HbA1c % in patients on Ch/S [8.7 (IQR 7.0-11.5) to 6.9 (IQR 6.3-9.2)] however it didn't reach statistical significance p = 0.225. Total insulin dose also decreased without statistical significance [33 IU (IQR 41-28) to 28 (IQR 23-35), p = 0.173]. The mean time in range (TIR) percent of the patients with AID systems were as follows; <54 mg/dL was 0.5 %, 56-70 mg/dL was 1.3 %, 70-180 mg/dL was 64.8 %, >180 mg/dL was 26.7 % and > 250 mg/dL was 6.7 %. CONCLUSION: Although AID systems are tested mostly in young type 1 patients our results show that elderly patients with brittle type 2 diabetes also benefit from an AID system. Even in very frail patients such as cancer patients, improvement can be seen.
Assuntos
Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Hipoglicemiantes , Sistemas de Infusão de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Idoso , Insulina/administração & dosagem , Insulina/uso terapêutico , Pessoa de Meia-Idade , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Glicemia/análise , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Peptídeo C/sangueRESUMO
BACKGROUND: Dysglycemia and insulin resistance increase type 2 diabetes (T2D) and cardiovascular disease (CVD) risk, yet associations with specific glucose-insulin homeostatic biomarkers have been inconsistent. Vitamin D and marine omega-3 fatty acids (n-3 FA) may improve insulin resistance. We sought to examine the association between baseline levels of insulin, C-peptide, HbA1c, and a novel insulin resistance score (IRS) with incident cardiometabolic diseases, and whether randomized vitamin D or n-3 FA modify these associations. METHODS: VITamin D and OmegA-3 TriaL (NCT01169259) was a randomized clinical trial testing vitamin D and n-3 FA for the prevention of CVD and cancer over a median of 5.3 years. Incident cases of T2D and CVD (including cardiovascular death, myocardial infarction, stroke, and coronary revascularization) were matched 1:1 on age, sex, and fasting status to controls. Conditional logistic regressions adjusted for demographic, clinical, and adiposity-related factors were used to assess the adjusted odds ratio (aOR) per-standard deviation (SD) and 95%CI of baseline insulin, C-peptide, HbA1c, and IRS (Insulin×0.0295 + C-peptide×0.00372) with risk of T2D, CVD, and coronary heart disease (CHD). RESULTS: We identified 218 T2D case-control pairs and 715 CVD case-control pairs including 423 with incident CHD. Each of the four biomarkers at baseline was separately associated with incident T2D, aOR (95%CI) per SD increment: insulin 1.46 (1.03, 2.06), C-peptide 2.04 (1.35, 3.09), IRS 1.72 (1.28, 2.31) and HbA1c 7.00 (3.76, 13.02), though only HbA1c remained statistically significant with mutual adjustments. For cardiovascular diseases, we only observed significant associations of HbA1c with CVD (1.19 [1.02, 1.39]), and IRS with CHD (1.25 [1.04, 1.50]), which persisted after mutual adjustment. Randomization to vitamin D and/or n-3 FA did not modify the association of these biomarkers with the endpoints. CONCLUSIONS: Each of insulin, C-peptide, IRS, and HbA1c were associated with incident T2D with the strongest association noted for HbA1c. While HbA1c was significantly associated with CVD risk, a novel IRS appears to be associated with CHD risk. Neither vitamin D nor n-3 FA modified the associations between these biomarkers and cardiometabolic outcomes.
Assuntos
Biomarcadores , Glicemia , Peptídeo C , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Ácidos Graxos Ômega-3 , Hemoglobinas Glicadas , Resistência à Insulina , Insulina , Vitamina D , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Peptídeo C/sangue , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Suplementos Nutricionais , Método Duplo-Cego , Ácidos Graxos Ômega-3/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Homeostase , Incidência , Insulina/sangue , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Vitamina D/sangueRESUMO
BACKGROUND: To investigate the long-term effects of combining bone marrow mesenchymal stem cells (MSCs) with mononuclear cells (MCs) in the treatment of type 2 diabetes mellitus (T2DM). METHODS: T2DM patients were divided into the combination group (Dual MSC + MC, n = 33), the mononuclear cell group (MC-Only, n = 32) and the control group (Control, n = 31). All groups were treated with insulin and metformin. The Dual MSC + MC group additionally received MSC and MC infusion and the MC-Only group additionally received MC infusion. The patients were followed up for 8 years. The primary endpoint was the C-peptide area under the curve (C-p AUC) at 1 year. This study was registered with clinicaltrial.gov (NCT01719640). RESULTS: A total of 97 patients were included and 89 completed the follow-up. The area under the curve of C-peptide of the Dual MSC + MC group and the MC-Only group was significantly increased (50.6% and 32.8%, respectively) at 1 year. After eight years of follow-up, the incidence of macrovascular complications was 13.8% (p = 0.009) in the Dual MSC + MC group and 21.4% (p = 0.061) in the MC-Only group, while it was 44.8% in the Control group. The incidence of diabetic peripheral neuropathy (DPN) was 10.3% (p = 0.0015) in the Dual MSC + MC group, 17.9% (p = 0.015) in the MC-Only group, and 48.3% in the Control group. CONCLUSIONS: The combination of MSC and MC therapy can reduce the incidence of chronic diabetes complications and improves metabolic control with mild side effects in T2DM patients.
Assuntos
Diabetes Mellitus Tipo 2 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Diabetes Mellitus Tipo 2/terapia , Masculino , Feminino , Transplante de Células-Tronco Mesenquimais/métodos , Pessoa de Meia-Idade , Seguimentos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Leucócitos Mononucleares/metabolismo , Idoso , Peptídeo C/metabolismo , Peptídeo C/sangue , Adulto , Terapia CombinadaRESUMO
AIM/INTRODUCTION: Xanthine oxidoreductase (XOR) inhibitor treatment, which reduces reactive oxygen species (ROS) production and increases adenosine triphosphate (ATP) synthesis, has been reported to improve glycemic control. The possible protective effects of XOR inhibitor treatment on insulin secretory capacity were investigated in patients with type 2 diabetes. MATERIALS AND METHODS: This retrospective cross-sectional study included 428 patients with type 2 diabetes. Insulin secretory capacity was assessed based on fasting serum C-peptide concentration (CPR) and C-peptide index (CPI) in all subjects, while insulin resistance in non-insulin users (n = 312) was determined using the homeostasis model assessment of insulin resistance (HOMA-IR) index. RESULTS: Median values for CPR and CPI in all subjects were 2.4 ng/mL and 1.5, respectively, while that for HOMA-IR in non-insulin users was 3.2. The XOR inhibitor users (n = 72) had significantly (P < 0.001) higher CPR and CPI levels than non-users (n = 356). Multivariable regression analyses showed XOR inhibitor use was positively associated with CPR (ß = 0.153, P = 0.001) and CPI (ß = 0.144, P = 0.001). Similar results were observed in propensity score analyses. In subgroup analyses of patients with a preserved estimated glomerular filtration rate (≥60 mL/min/1.73 m2) and non-insulin users, these associations remained significant. Furthermore, the associations were significant in patients with lower (≤6.0 mg/dL) but not with higher (>6.0 mg/dL) uric acid levels (P for interaction <0.05). On the other hand, XOR inhibitor use showed no significant association with HOMA-IR. CONCLUSIONS: The results of XOR inhibitor treatment, especially a sufficient reduction in serum uric acid level, may provide protective effects on insulin secretory capacity in patients with type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Secreção de Insulina , Xantina Desidrogenase , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Feminino , Xantina Desidrogenase/antagonistas & inibidores , Estudos Retrospectivos , Estudos Transversais , Pessoa de Meia-Idade , Secreção de Insulina/efeitos dos fármacos , Insulina/uso terapêutico , Idoso , Inibidores Enzimáticos/uso terapêutico , Peptídeo C/sangue , Glicemia/análise , Biomarcadores/sangueRESUMO
Hyperuricemia is an objective risk factor of derangement of fasting serum glucose and type 2 diabetes (T2D), yet whether hyperuricemia has a causative influence on insulin resistance is still debatable. In this study, we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Patients with renal stone and hyperuricemia (n=15) were recruited from the private clinic of Ib-Sina Local Teaching Hospital in Mosul city and prospectively placed on allopurinol (300mg/day) for 6 months. Serum uric acid (SUA), fasting serum glucose (FSG), fasting insulin, and C-peptide were measured using commercial kits. Results confirmed that allopurinol has significantly (P<0.05) reduced c-peptide and insulin together with a non-significant (p>0.05) reduction of serum glucose levels. In conclusion, allopurinol has improved insulin level and glycemic control in a healthy individual, these findings could be used as a template for using allopurinol in diabetic patients to improve glycemic control or future studies could be directed toward structural modification of allopurinol which hopefully might lead to innovation of new antidiabetic drugs.