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1.
Diabetes Metab Res Rev ; 40(5): e3826, 2024 Jul.
Article En | MEDLINE | ID: mdl-38824455

INTRODUCTION: Early and tight glycaemic control is crucial to prevent long-term complications of Type 1 Diabetes (T1D). The aim of our study was to compare glucose metrics, including Time In Tight Range (TITR), in a real-world setting. METHODS: We performed a single-centre cross-sectional study in 534 children and adolescents with T1D. Participants were divided into four groups (multiple daily injections + real-time Continuous glucose monitoring (CGM), multiple daily injections + intermittently scanned CGM, sensor augmented pump (SAP), and Advanced Hybrid Closed-Loop (AHCL). Demographical and clinical data were collected and analysed. RESULTS: The group with AHCL showed significantly higher Time In Range (TIR) (71.31% ± 10.88) than SAP (57.82% ± 14.98; p < 0.001), MDI + rtCGM (54.56% ± 17.04; p < 0.001) and MDI + isCGM (52.17% ± 19.36; p < 0.001) groups with a lower Time Above Range (p < 0.001). The group with AHCL also showed lower Time Below Range than MDI + isCGM and SAP groups (p < 0.01). The overall TITR was 37% ± 14 with 19% of participants who reached a TITR ≥50% with a mean TIR of 81%. AHCL had significantly higher TITR (45.46% ± 11.77) than SAP (36.25% ± 13.53; p < 0.001), MDI + rtCGM (34.03% ± 13.89; p < 0.001) and MDI + isCGM (33.37% ± 15.84; p < 0.001) groups with a lower Coefficient of Variation (p < 0.001). CONCLUSIONS: Our study indicates that AHCL ensures a better glycaemic control with an improvement in both TIR and TITR, along with a reduction in CV. Implementation of automated insulin delivery systems should be considered in the treatment of children and adolescents with T1D.


Blood Glucose Self-Monitoring , Blood Glucose , Diabetes Mellitus, Type 1 , Hypoglycemic Agents , Insulin Infusion Systems , Insulin , Humans , Diabetes Mellitus, Type 1/drug therapy , Cross-Sectional Studies , Child , Adolescent , Female , Male , Blood Glucose Self-Monitoring/methods , Blood Glucose/analysis , Insulin/administration & dosage , Insulin/therapeutic use , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Glycemic Control/methods , Glycated Hemoglobin/analysis , Follow-Up Studies , Prognosis , Biomarkers/analysis , Hypoglycemia/prevention & control
2.
Am J Nurs ; 124(6): 61, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38780343

According to this study: In adults with type 1 diabetes, continuous glucose monitoring (CGM) was associated with lower odds of developing diabetic retinopathy and proliferative diabetic retinopathy.No associations were found between CGM use, insulin pump use, or the use of both CGM and an insulin pump with progression of diabetic retinopathy.


Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 1 , Diabetic Retinopathy , Humans , Diabetic Retinopathy/prevention & control , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Male , Female , Adult , Middle Aged , Blood Glucose/analysis , Insulin Infusion Systems , Risk Factors , Continuous Glucose Monitoring
3.
Front Immunol ; 15: 1366335, 2024.
Article En | MEDLINE | ID: mdl-38707904

Background: Immune checkpoint inhibitors (ICPis) induce autoimmune diseases, including autoimmune polyendocrine syndrome type 2 (APS-2), which is defined as a combination of at least two of the following endocrinopathies: autoimmune thyroid disease, type 1 diabetes, and Addison's disease. Cases with the full triad are rare. We present a case of an elderly woman who developed APS-2 with the complete triad shortly after starting anti-programmed cell death 1 (anti-PD1) treatment and review the related literature. Case: A 60-year-old woman, without any personal or family history of autoimmune and endocrine diseases, started the immunotherapy of anti-PD1 (camrelizumab) for squamous cell carcinoma of the urethral meatus. She developed primary hypothyroidism with elevated antibodies to thyroid peroxidase and thyroglobulin after 25 weeks of treatment, and developed primary adrenal insufficiency with adrenal crisis and fulminant type 1 diabetes with ketoacidosis after 45 weeks. Therefore, this patient met the diagnosis of APS-2 and was given multiple hormone replacement including glucocorticoid, levothyroxine and insulin therapy. Continuous improvement was achieved through regular monitoring and titration of the dosage. Conclusions: Different components of APS-2 may appear at different time points after anti-PD1 administration, and can be acute and life-threatening. A good prognosis can be obtained by appropriate replacement with multiple hormones. Insights: With the clinical application of ICPis to APS-2, the complexity of its treatment should be paid enough attention.


Immune Checkpoint Inhibitors , Polyendocrinopathies, Autoimmune , Humans , Female , Polyendocrinopathies, Autoimmune/drug therapy , Polyendocrinopathies, Autoimmune/diagnosis , Middle Aged , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/chemically induced , Diabetes Mellitus, Type 1/diagnosis
4.
Comb Chem High Throughput Screen ; 27(5): 786-796, 2024.
Article En | MEDLINE | ID: mdl-38773797

OBJECTIVE: Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary osteoporosis and is the main cause of bone fragility and fractures in many patients with diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve DOP by inhibiting autophagy and oxidative stress. METHODS: Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model (MC3T3-E1) was induced using high glucose levels. RESULTS: After ZYBSF treatment, bone microstructure significantly improved. The bone mineral density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly increased. After ZYBSF treatment, the femur structure of the rats was relatively intact, collagen fibers were significantly increased, and osteoporosis was significantly improved. A total of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments, ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p-ERK. CONCLUSION: ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling pathway.


Autophagy , Drugs, Chinese Herbal , Osteoporosis , Oxidative Stress , Animals , Autophagy/drug effects , Oxidative Stress/drug effects , Osteoporosis/drug therapy , Osteoporosis/metabolism , Rats , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Mice , Diabetes Mellitus, Experimental/drug therapy , Male , Rats, Sprague-Dawley , Streptozocin , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/complications , Bone Density/drug effects
6.
Diabetes Metab Res Rev ; 40(4): e3806, 2024 May.
Article En | MEDLINE | ID: mdl-38757421

BACKGROUND: The management of Type 1 Diabetes Mellitus (T1DM) is a significant clinical challenge. This study evaluated the efficacy of teplizumab, an immunomodulatory drug, in patients with T1DM, using a systematic review and meta-analysis approach. METHODS: We systematically searched multiple databases including Medline, Scopus, and others up to 10 January 2024, without language or regional restrictions. We included randomized controlled trials (RCTs) comparing teplizumab with placebo in T1DM patients. RESULTS: Our analysis incorporated 8 RCTs, predominantly involving participants aged 7-35 years, diagnosed with T1DM and treated with 14-day courses of teplizumab. The primary outcomes included insulin use, C-peptide levels, and HbA1c levels. We observed a significant reduction in insulin use in the teplizumab group standardised mean difference of -0.50 (95% Confidence Interval [CI]: -0.76 to -0.23, p < 0.001; I2 = 49%). C-peptide levels were consistently higher in the teplizumab group, indicating improved endogenous insulin production. However, no significant change was noted in HbA1c levels between the groups. Quality assessment indicated a low risk of bias in most studies. CONCLUSIONS: Teplizumab has a significant impact on reducing insulin dependence and enhancing endogenous insulin production in T1DM patients. However, its effect on long-term glycaemic control, as indicated by HbA1c levels, remains inconclusive.


Antibodies, Monoclonal, Humanized , Diabetes Mellitus, Type 1 , Randomized Controlled Trials as Topic , Adolescent , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Diabetes Mellitus, Type 1/drug therapy , Glycated Hemoglobin/analysis , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Prognosis , Treatment Outcome , Child , Young Adult , Adult
7.
Tunis Med ; 102(4): 235-240, 2024 Apr 05.
Article Fr | MEDLINE | ID: mdl-38746964

INTRODUCTION-AIM: Flexible insulin therapy is currently considered the gold standard therapy of type 1 diabetes. We aimed to study the evolution of glycemic control, weight and nutritional intake of a group of patients with type 1 diabetes, three months after the initiation of functional insulin therapy (FIT). METHODS: This was a prospective longitudinal study having included 30 type 1 diabetic patients hospitalized for education to FIT. Each patient underwent an assessment of glycemic control (glycated hemoglobin (A1C) and number of hypoglycemia), weight and nutritional intake before FIT and 3 months after the initiation of this educative approach. RESULTS: The mean age of patients was 21,8 ± 7,9 years and the sex ratio was 0,5. The mean duration of diabetes was 7,2 ± 6 years. Three months after initiation of FIT, we observed a significant lowering of A1C, which went from 9,2 ± 1,6% to 8,3 ± 1,4% (p<0,001) of the number of minor hypoglycemia (p=0,001) and that of severe hypoglycemia (p= 0,021). the average weight went from 64,6 ± 13,1 kg to 65,5 ± 13,5 kg (p = 0,040) with a significant increase in BMI (p = 0,041). Weight gain was observed in 67% of patients. This weight gain contrasted with a significant decrease in caloric (p = 0,040) and in carbohydrates intakes (p = 0,027). CONCLUSION: Weight gain, associated with better glycemic control, should encourage the healthcare team to strengthen therapeutic education of patients undergoing FIT in order to limit weight gain.


Body Weight , Diabetes Mellitus, Type 1 , Hypoglycemic Agents , Insulin , Humans , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Female , Male , Insulin/administration & dosage , Insulin/therapeutic use , Adult , Young Adult , Prospective Studies , Longitudinal Studies , Adolescent , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Body Weight/physiology , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Hypoglycemia/prevention & control , Hypoglycemia/chemically induced , Hypoglycemia/epidemiology , Glycemic Control/methods , Energy Intake , Weight Gain/physiology , Weight Gain/drug effects , Time Factors , Blood Glucose/analysis , Blood Glucose/metabolism
8.
Andes Pediatr ; 95(2): 183-189, 2024 Apr.
Article Es | MEDLINE | ID: mdl-38801366

Diabetic ketoacidosis (DKA) is one of the most serious complications of type 1 diabetes mellitus. Its treatment requires fluid and electrolyte replacement and insulin. Hypophosphatemia as a complication of treatment has been scarcely evaluated. OBJECTIVES: To estimate the incidence of hypophosphatemia in children with DKA, treated with subcutaneous regular insulin (IRS), and to explore factors associated with this complication. PATIENTS AND METHOD: Prospective, observational study. Patients diagnosed with DKA hospitalized in the general care ward were included. Data on phosphatemia, glycemia, acid-base status, and IRS amount (U/kg) received were recorded at baseline and after 24 h of treatment. Hypophosphatemia was defined as values below 2.5 mg/dl. The correlation between initial phosphate and at 24 h of treatment was evaluated; the incidence of hypophosphatemia at 24 h was expressed as a percentage of the total number of patients. RESULTS: 30 patients were included, 15 were female, mean age 11.4 ± 3.2 years. At 24 h of treatment with IRS, 36.7% (95%CI 22-55%) presented hypophosphatemia, mean value 1.9 ± 1.5 mg/dl. Initial bicarbonate < 10 mmol/L acted as a predictor of hypophosphatemia (OR 7.5; 95%CI 1.4-39.8%; p = 0.01). No patient required intravenous phosphate correction, and no associated clinical complications were observed. CONCLUSION: In the group studied, the incidence of hypophosphatemia reached 36.7% at 24 hours of treatment. Initial bicarbonate lower than 10 mmol/L was significantly associated with hypophosphatemia. No complications associated with hypophosphatemia were observed.


Diabetic Ketoacidosis , Hypoglycemic Agents , Hypophosphatemia , Insulin , Humans , Female , Hypophosphatemia/epidemiology , Hypophosphatemia/etiology , Male , Diabetic Ketoacidosis/epidemiology , Child , Prospective Studies , Insulin/therapeutic use , Adolescent , Injections, Subcutaneous , Prevalence , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/drug therapy , Incidence
9.
Trials ; 25(1): 331, 2024 May 21.
Article En | MEDLINE | ID: mdl-38773658

BACKGROUND: Self-monitoring of glucose is an essential component of type 1 diabetes (T1D) management. In recent years, continuous glucose monitoring (CGM) has provided an alternative to daily fingerstick testing for the optimisation of insulin dosing and general glucose management in people with T1D. While studies have been conducted to evaluate the impact of CGM on clinical outcomes in the US, Europe and Australia, there are limited data available for low- and middle-income countries (LMICs) and further empirical evidence is needed to inform policy decision around their use in these countries. METHODS: This trial was designed as a pragmatic, parallel-group, open-label, multicentre, three-arm, randomised (1:1:1) controlled trial of continuous or periodic CGM device use versus standard of care in people with T1D in South Africa and Kenya. The primary objective of this trial will be to assess the impact of continuous or periodic CGM device use on glycaemic control as measured by change from baseline glycosylated haemoglobin (HbA1c). Additional assessments will include clinical outcomes (glucose variation, time in/below/above range), safety (adverse events, hospitalisations), quality of life (EQ-5D, T1D distress score, Glucose Monitoring Satisfaction Survey for T1D), and health economic measures (incremental cost-effectiveness ratios, quality adjusted life years). DISCUSSION: This trial aims to address the substantial evidence gap on the impact of CGM device use on clinical outcomes in LMICs, specifically South Africa and Kenya. The trial results will provide evidence to inform policy and treatment decisions in these countries. TRIAL REGISTRATION: NCT05944731 (Kenya), July 6, 2023; NCT05944718 (South Africa), July 13, 2023.


Blood Glucose Self-Monitoring , Blood Glucose , Diabetes Mellitus, Type 1 , Glycated Hemoglobin , Multicenter Studies as Topic , Pragmatic Clinical Trials as Topic , Humans , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/diagnosis , Blood Glucose Self-Monitoring/instrumentation , Kenya , Blood Glucose/metabolism , Blood Glucose/analysis , Blood Glucose/drug effects , Glycated Hemoglobin/metabolism , Glycated Hemoglobin/analysis , South Africa , Quality of Life , Glycemic Control/instrumentation , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Implementation Science , Insulin/administration & dosage , Insulin/therapeutic use , Treatment Outcome , Cost-Benefit Analysis , Continuous Glucose Monitoring
11.
Lancet Diabetes Endocrinol ; 12(6): 390-403, 2024 Jun.
Article En | MEDLINE | ID: mdl-38697182

BACKGROUND: Advanced hybrid closed loop (AHCL) therapy can improve glycaemic control in pregnant women with type 1 diabetes. However, data are needed on the efficacy and safety of AHCL systems as these systems, such as the MiniMed 780G, are not currently approved for use in pregnant women. We aimed to investigate whether the MiniMed 780G can improve glycaemic control with less hypoglycaemia in pregnant women with type 1 diabetes. METHODS: CRISTAL was a double-arm, parallel-group, open-label, randomised controlled trial conducted in secondary and tertiary care specialist endocrinology centres at 12 hospitals (11 in Belgium and one in the Netherlands). Pregnant women aged 18-45 years with type 1 diabetes were randomly assigned (1:1) to AHCL therapy (MiniMed 780G) or standard insulin therapy (standard of care) at a median of 10·1 (IQR 8·6-11·6) weeks of gestation. Randomisation was done centrally with minimisation dependent on baseline HbA1c, insulin administration method, and centre. Participants and study teams were not masked to group allocation. The primary outcome was proportion of time spent in the pregnancy-specific target glucose range (3·5-7·8 mmol/L), measured by continuous glucose monitoring (CGM) at 14-17 weeks, 20-23 weeks, 26-29 weeks, and 33-36 weeks. Key secondary outcomes were overnight time in target range, and time below glucose range (<3·5 mmol/L) overall and overnight. Analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT04520971). FINDINGS: Between Jan 15, 2021 and Sept 30, 2022, 101 participants were screened, and 95 were randomly assigned to AHCL therapy (n=46) or standard insulin therapy (n=49). 43 patients assigned to AHCL therapy and 46 assigned to standard insulin therapy completed the study. At baseline, 91 (95·8%) participants used insulin pumps, and the mean HbA1c was 6·5% (SD 0·6). The mean proportion of time spent in the target range (averaged over four time periods) was 66·5% (SD 10·0) in the AHCL therapy group compared with 63·2% (12·4) in the standard insulin therapy group (adjusted mean difference 1·88 percentage points [95% CI -0·82 to 4·58], p=0·17). Overnight time in the target range was higher (adjusted mean difference 6·58 percentage points [95% CI 2·31 to 10·85], p=0·0026), and time below range overall (adjusted mean difference -1·34 percentage points [95% CI, -2·19 to -0·49], p=0·0020) and overnight (adjusted mean difference -1·86 percentage points [95% CI -2·90 to -0·81], p=0·0005) were lower with AHCL therapy than with standard insulin therapy. Participants assigned to AHCL therapy reported higher treatment satisfaction. No unanticipated safety events occurred with AHCL therapy. INTERPRETATION: In pregnant women starting with tighter glycaemic control, AHCL therapy did not improve overall time in target range but improved overnight time in target range, reduced time below range, and improved treatment satisfaction. These data suggest that the MiniMed 780G can be safely used in pregnancy and provides some additional benefits compared with standard insulin therapy; however, it will be important to refine the algorithm to better align with pregnancy requirements. FUNDING: Diabetes Liga Research Fund and Medtronic.


Blood Glucose , Diabetes Mellitus, Type 1 , Hypoglycemic Agents , Insulin Infusion Systems , Insulin , Pregnancy in Diabetics , Humans , Female , Pregnancy , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Adult , Insulin/administration & dosage , Insulin/therapeutic use , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/administration & dosage , Pregnancy in Diabetics/drug therapy , Pregnancy in Diabetics/blood , Blood Glucose/analysis , Blood Glucose/drug effects , Young Adult , Adolescent , Hypoglycemia/chemically induced , Glycemic Control/methods , Blood Glucose Self-Monitoring/methods
12.
BMJ Open Diabetes Res Care ; 12(3)2024 May 15.
Article En | MEDLINE | ID: mdl-38749509

INTRODUCTION: Manufacturer-supported didactic teaching programmes offer effective automated insulin delivery (AID) systems onboarding in children and young people (CYP) with type 1 diabetes (T1D). However, this approach has limited flexibility to accommodate the needs of families requiring additional support. RESEARCH DESIGN AND METHODS: Evaluate the efficacy of an inperson manufacturer-supported didactic teaching programme (Group A), in comparison to a flexible flipped learning approach delivered virtually or inperson (Group B). Retrospective analysis of CYP with T1D using continuous glucose monitoring (CGM), who were initiated on AID systems between 2021 and 2023. Compare CGM metrics from baseline to 90 days for both groups A and B. Additionally, compare the two groups for change in CGM metrics over the 90-day period (∆), patient demographics and onboarding time. RESULTS: Group A consisted of 74 CYP (53% male) with median age of 13.9 years and Group B 91 CYP (54% male) with median age of 12.7 years. From baseline to 90 days, Group A lowered mean (±SD) time above range (TAR, >10.0 mmol/L) from 47.6% (±15.0) to 33.2% (±15.0) (p<0.001), increased time in range (TIR, 3.9-10.0 mmol/L) from 50.4% (±14.0) to 64.7% (±10.2) (p<0.001). From baseline to 90 days, Group B lowered TAR from 51.3% (±15.1) to 34.5% (±11.3) (p<0.001) and increased TIR from 46.5% (±14.5) to 63.7% (±11.0) (p<0.001). There was no difference from baseline to 90 days for time below range (TBR, <3.9 mmol/L) for Group A and Group B. ∆ TAR, TIR and TBR for both groups were comparable. Group B consisted of CYP with higher socioeconomic deprivation, greater ethnic diversity and lower carer education achievement (p<0.05). The majority of Group B (n=79, 87%) chose virtual flipped learning, halving diabetes educator time and increasing onboarding cadence by fivefold. CONCLUSIONS: A flexible virtual flipped learning programme increases onboarding cadence and capacity to offer equitable AID system onboarding.


Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 1 , Hypoglycemic Agents , Insulin Infusion Systems , Insulin , Humans , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Male , Child , Adolescent , Female , Insulin/administration & dosage , Insulin/therapeutic use , Retrospective Studies , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Blood Glucose Self-Monitoring/methods , Blood Glucose/analysis , Ethnicity , Socioeconomic Factors , Follow-Up Studies , Health Services Accessibility
13.
Biomed Pharmacother ; 175: 116731, 2024 Jun.
Article En | MEDLINE | ID: mdl-38761421

Nutraceuticals have gained increasing interest, prompting the need to investigate plant extracts for their beneficial properties and potential side effects. This study aimed to assess the nutraceutical effects of environmentally clean extracts from Rosmarinus officinalis and Gongolaria abies-marina (formerly Cystoseira abies-marina (Phaeophyceae)) on the metabolic profile of streptozotocin-induced diabetic rats. We conducted untargeted LC-QTOF-MS metabolic profiling on six groups of rats: three diabetic groups receiving either a placebo, R. officinalis, or G. abies-marina extracts, and three corresponding control groups. The metabolic analysis revealed significant alterations in the levels of various glycerophospholipids, sterol lipids, and fatty acyls. Both extracts influenced the metabolic profile, partially mitigating diabetes-induced changes. Notably, G. abies-marina extract had a more pronounced impact on the animals' metabolic profiles compared to R. officinalis. In conclusion, our findings suggest that environmentally clean extracts from R. officinalis and G. abies-marina possess nutraceutical potential, as they were able to modulate the metabolic profile in streptozotocin-induced diabetic rats. G. abies-marina extract exhibited a more substantial effect on metabolic alterations induced by diabetes compared to R. officinalis. These results warrant further exploration of these plant extracts for their potential in managing diabetes-related metabolic disturbances.


Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Dietary Supplements , Plant Extracts , Rosmarinus , Animals , Plant Extracts/pharmacology , Rosmarinus/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Male , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/metabolism , Rats , Rats, Wistar , Metabolomics , Metabolome/drug effects , Blood Glucose/drug effects , Blood Glucose/metabolism , Streptozocin , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/isolation & purification
14.
Proc Natl Acad Sci U S A ; 121(23): e2401458121, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38809711

Patients with type 1 diabetes mellitus who are dependent on an external supply of insulin develop insulin-derived amyloidosis at the sites of insulin injection. A major component of these plaques is identified as full-length insulin consisting of the two chains A and B. While there have been several reports that characterize insulin misfolding and the biophysical properties of the fibrils, atomic-level information on the insulin fibril architecture remains elusive. We present here an atomic resolution structure of a monomorphic insulin amyloid fibril that has been determined using magic angle spinning solid-state NMR spectroscopy. The structure of the insulin monomer yields a U-shaped fold in which the two chains A and B are arranged in parallel to each other and are oriented perpendicular to the fibril axis. Each chain contains two ß-strands. We identify two hydrophobic clusters that together with the three preserved disulfide bridges define the amyloid core structure. The surface of the monomeric amyloid unit cell is hydrophobic implicating a potential dimerization and oligomerization interface for the assembly of several protofilaments in the mature fibril. The structure provides a starting point for the development of drugs that bind to the fibril surface and disrupt secondary nucleation as well as for other therapeutic approaches to attenuate insulin aggregation.


Amyloid , Insulin , Humans , Amyloid/chemistry , Amyloid/metabolism , Insulin/chemistry , Insulin/metabolism , Models, Molecular , Hydrophobic and Hydrophilic Interactions , Diabetes Mellitus, Type 1/drug therapy , Protein Conformation , Magnetic Resonance Spectroscopy
15.
BMJ Open ; 14(5): e075554, 2024 May 06.
Article En | MEDLINE | ID: mdl-38719319

OBJECTIVES: To assess the feasibility and change in clinical outcomes associated with continuous glucose monitoring (CGM) use among a rural population in Malawi living with type 1 diabetes. DESIGN: A 2:1 open randomised controlled feasibility trial. SETTING: Two Partners In Health-supported Ministry of Health-run first-level district hospitals in Neno, Malawi. PARTICIPANTS: 45 people living with type 1 diabetes (PLWT1D). INTERVENTIONS: Participants were randomly assigned to Dexcom G6 CGM (n=30) use or usual care (UC) (n=15) consisting of Safe-Accu glucose monitors and strips. Both arms received diabetes education. OUTCOMES: Primary outcomes included fidelity, appropriateness and severe adverse events. Secondary outcomes included change in haemoglobin A1c (HbA1c), acceptability, time in range (CGM arm only) SD of HbA1c and quality of life. RESULTS: Participants tolerated CGM well but were unable to change their own sensors which resulted in increased clinic visits in the CGM arm. Despite the hot climate, skin rashes were uncommon but cut-out tape overpatches were needed to secure the sensors in place. Participants in the CGM arm had greater numbers of dose adjustments and lifestyle change suggestions than those in the UC arm. Participants in the CGM arm wore their CGM on average 63.8% of the time. Participants in the UC arm brought logbooks to clinic 75% of the time. There were three hospitalisations all in the CGM arm, but none were related to the intervention. CONCLUSIONS: This is the first randomised controlled trial conducted on CGM in a rural region of a low-income country. CGM was feasible and appropriate among PLWT1D and providers, but inability of participants to change their own sensors is a challenge. TRIAL REGISTRATION NUMBER: PACTR202102832069874.


Blood Glucose Self-Monitoring , Blood Glucose , Diabetes Mellitus, Type 1 , Feasibility Studies , Glycated Hemoglobin , Hospitals, District , Humans , Malawi , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Female , Male , Blood Glucose Self-Monitoring/methods , Adult , Glycated Hemoglobin/analysis , Blood Glucose/analysis , Middle Aged , Quality of Life , Rural Population , Continuous Glucose Monitoring
16.
Peptides ; 177: 171214, 2024 Jul.
Article En | MEDLINE | ID: mdl-38615716

In this systematic review, we assessed the safety and possible safety events of native glucose-dependent insulinotropic polypeptide (GIP)(1-42) in human studies with administration of synthetic human GIP. We searched the PubMed database for all trials investigating synthetic human GIP(1-42) administration. A total of 67 studies were included. Study duration ranged from 30 min to 6 days. In addition to healthy individuals, the studies included individuals with impaired glucose tolerance, type 2 diabetes, type 1 diabetes, chronic pancreatitis and secondary diabetes, latent autoimmune diabetes in adults, diabetes caused by a mutation in the hepatocyte nuclear factor 1-alpha gene, end-stage renal disease, chronic renal insufficiency, critical illness, hypoparathyroidism, or cystic fibrosis-related diabetes. Of the included studies, 78% did not mention safety events, 10% of the studies reported that no safety events were observed in relation to GIP administration, and 15% of the studies reported safety events in relation to GIP administration with most frequently reported event being a moderate and transient increased heart rate. Gastrointestinal safety events, and changes in blood pressure were also reported. Plasma concentration of active GIP(1-42) increased linearly with dose independent of participant phenotype. There was no significant correlation between achieved maximal concentration of GIP(1-42) and reported safety events. Clearance rates of GIP(1-42) were similar between participant groups. In conclusion, the available data indicate that GIP(1-42) in short-term (up to 6 days) infusion studies is generally well-tolerated. The long-term safety of continuous GIP(1-42) administration is unknown.


Gastric Inhibitory Polypeptide , Humans , Peptide Fragments , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Glucose Intolerance/metabolism , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/metabolism
17.
Nutr Diabetes ; 14(1): 23, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38653987

BACKGROUND: The number of patients with type 1 diabetes rises rapidly around the world in recent years. Maternal diabetes has a detrimental effect on reproductive outcomes due to decreased oocyte quality. However, the strategies to improve the oocyte quality and artificial reproductive technology (ART) efficiency of infertile females suffering from diabetes have not been fully studied. In this study, we aimed to examine the effects of nicotinamide mononucleotide (NMN) on oocyte maturation of mouse with type 1 diabetes mouse and explore the underlying mechanisms of NMN's effect. METHODS: Streptozotocin (STZ) was used to establish the mouse models with type 1 diabetes. The successful establishment of the models was confirmed by the results of body weight test, fasting blood glucose test and haematoxylin and eosin (H&E) staining. The in vitro maturation (IVM) rate of oocytes from diabetic mice was examined. Immunofluorescence staining (IF) was performed to examine the reactive oxygen species (ROS) level, spindle/chromosome structure, mitochondrial function, actin dynamics, DNA damage and histone modification of oocytes, which are potential factors affecting the oocyte quality. The quantitative reverse transcription PCR (RT-qPCR) was used to detect the mRNA levels of Sod1, Opa1, Mfn2, Drp1, Sirt1 and Sirt3 in oocytes. RESULTS: The NMN supplementation increased the oocyte maturation rate of the mice with diabetes. Furthermore, NMN supplementation improved the oocyte quality by rescuing the actin dynamics, reversing meiotic defects, improving the mitochondrial function, reducing ROS level, suppressing DNA damage and restoring changes in histone modifications of oocytes collected from the mice with diabetes. CONCLUSION: NMN could improve the maturation rate and quality of oocytes in STZ-induced diabetic mice, which provides a significant clue for the treatment of infertility of the patients with diabetes.


Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Dynamins , Nicotinamide Mononucleotide , Oocytes , Reactive Oxygen Species , Animals , Mice , Female , Oocytes/drug effects , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Experimental/drug therapy , Reactive Oxygen Species/metabolism , Nicotinamide Mononucleotide/pharmacology , Mitochondria/drug effects , Mitochondria/metabolism , Sirtuin 1/metabolism , Sirtuin 3/metabolism , In Vitro Oocyte Maturation Techniques/methods , Superoxide Dismutase-1 , DNA Damage/drug effects , Streptozocin , Oogenesis/drug effects
18.
Artif Intell Med ; 151: 102868, 2024 May.
Article En | MEDLINE | ID: mdl-38632030

Proper insulin management is vital for maintaining stable blood sugar levels and preventing complications associated with diabetes. However, the soaring costs of insulin present significant challenges to ensuring affordable management. This paper conducts a comprehensive review of current literature on the application of machine learning (ML) in insulin management for diabetes patients, particularly focusing on enhancing affordability and accessibility within the United States. The review encompasses various facets of insulin management, including dosage calculation and response, prediction of blood glucose and insulin sensitivity, initial insulin estimation, resistance prediction, treatment adherence, complications, hypoglycemia prediction, and lifestyle modifications. Additionally, the study identifies key limitations in the utilization of ML within the insulin management literature and suggests future research directions aimed at furthering accessible and affordable insulin treatments. These proposed directions include exploring insurance coverage, optimizing insulin type selection, assessing the impact of biosimilar insulin and market competition, considering mental health factors, evaluating insulin delivery options, addressing cost-related issues affecting insulin usage and adherence, and selecting appropriate patient cost-sharing programs. By examining the potential of ML in addressing insulin management affordability and accessibility, this work aims to envision improved and cost-effective insulin management practices. It not only highlights existing research gaps but also offers insights into future directions, guiding the development of innovative solutions that have the potential to revolutionize insulin management and benefit patients reliant on this life-saving treatment.


Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Insulin , Machine Learning , Humans , Blood Glucose/metabolism , Blood Glucose/analysis , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/economics , Insulin/economics , Insulin/metabolism , Insulin/therapeutic use
19.
Indian Pediatr ; 61(5): 486-488, 2024 May 15.
Article En | MEDLINE | ID: mdl-38655887

Children and adolescents with Type 1 diabetes (T1D) require bolus insulin before each meal, necessitating self-care activities including blood glucose checking to determine insulin dose (or check for hypoglycemia) and injecting insulin during school hours. Though these activities are essential for optimizing glycemic control, they are met with reluctance from parents, the child, school authorities, and sometimes peers. This requires ongoing education and support for the child, school staff, and other students, by the diabetes care team. Many problems of performing self-care activities can be greatly reduced by allowing them in the child's classroom itself, a strategy which offers several logistical, safety, psychological and social benefits. The glucometer and strips, continuous glucose monitoring device, insulin in a cool case, and hypoglycemia kit are kept in the teacher's custody, and used by the child as needed, under supervision. This normalizes diabetes and its care, obviates concealment of diabetes, enhances the child's and teacher's confidence, optimizes diabetes care by ensuring timely and consistent insulin dosing, encourages hypoglycemia prevention and management, and reduces the chances of the child being bullied. It also promotes acceptance of diabetes by peers and greater community awareness. Other places for self-care like the medical room or the toilet have disadvantages. Possible limitations of this strategy could be objections occasionally raised by some school staff, lack of privacy needed by adolescents, or bullying by classmates: issues which need proactive handling. The diabetes care team may do well to emphasize performing self-care activities in the classroom, working with school staff and parents to this end.


Diabetes Mellitus, Type 1 , Schools , Self Care , Humans , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Self Care/methods , Child , Adolescent , Insulin/administration & dosage , Insulin/therapeutic use , Blood Glucose Self-Monitoring/methods
20.
Front Endocrinol (Lausanne) ; 15: 1352302, 2024.
Article En | MEDLINE | ID: mdl-38559693

Blood glucose monitoring constitutes a pivotal element in the clinical management of Type 1 diabetes (T1D), a globally escalating metabolic disorder. Continuous glucose monitoring (CGM) devices have demonstrated efficacy in optimizing glycemic control, mitigating adverse health outcomes, and augmenting the overall quality of life for individuals afflicted with T1D. Recent progress in the field encompasses the refinement of electrochemical sensors, which enhances the effectiveness of blood glucose monitoring. This progress empowers patients to assume greater control over their health, alleviating the burdens associated with their condition, and contributing to the overall alleviation of the healthcare system. The introduction of novel medical devices, whether derived from existing prototypes or originating as innovative creations, necessitates adherence to a rigorous approval process regulated by the Food and Drug Administration (FDA). Diverse device classifications, stratified by their associated risks, dictate distinct approval pathways, each characterized by varying timelines. This review underscores recent advancements in blood glucose monitoring devices primarily based on electrochemical sensors and elucidates their regulatory journey towards FDA approval. The advent of innovative, non-invasive blood glucose monitoring devices holds promise for maintaining stringent glycemic control, thereby preventing T1D-associated comorbidities, and extending the life expectancy of affected individuals.


Diabetes Mellitus, Type 1 , United States/epidemiology , Humans , Diabetes Mellitus, Type 1/drug therapy , Blood Glucose , Blood Glucose Self-Monitoring , Quality of Life , United States Food and Drug Administration
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