Effect of treadmill ambulatory training on glucose control and blood pressure in persons with type 2 diabetes: A pilot study.

BACKGROUND: Lack of time is often cited by persons with type 2 diabetes for non-participation in regular exercise. This highlights the need to explores ways to help persons with type 2 diabetes to engage in an active lifestyle. This study evaluated the effect of a short duration norm intensity exercise on blood glucose and blood pressure in persons with type 2 diabetes. METHODS: Twenty persons with type 2 diabetes were randomly assigned to either training group (n = 10) or control group (n = 10). The training group received 4-weeks ambulatory training on a motor-driven treadmill (2 x 20 min per week at 60% target heart rate). The control group received no training. Blood glucose, and systolic and diastolic blood pressures were assessed before and after the 4-weeks training. Repeated measures ANOVA were used to examine training effect. RESULTS: Training significantly improved blood glucose (mean difference = -2.73; p = 0.03). No effects were found for systolic blood pressure (mean difference = -0.30; p = 0.96) and diastolic blood pressure (mean difference = -0.90; p = 0.82). CONCLUSION: Training improved blood glucose but not blood pressure. A short-duration ambulatory training is an appropriate exercise mode to elicit beneficial effect, and exercise adoption in persons with type 2 diabetes. TRIAL REGISTRATION: This pilot trial is registered with the Pan African Clinical Trial Registry at pactr.samrc.ac.za (PACTR202306601940612).

Diabetes Mellitus gestacional: perfil epidemiológico de maternidade de alto risco / Gestational Diabetes Mellitus: epidemiological profile of high- risk maternity / Diabetes Mellitus gestacional: perfil epidemiológico de una maternidad de alto riesgo

O Diabetes Mellitus Gestacional é definido como doença que se caracteriza pelos altos níveis de glicemia sanguínea, diagnosticada durante a gestação. Este adoecimento pode acarretar várias complicações maternas e fetais, muitas vezes, necessitando de internamento precoce e cuidados avançados. Objetivou-se caracterizar o perfil epidemiológico de gestantes com diabetes mellitus gestacionais atendidas em serviço de referência. Trata-se de estudo descritivo, documental, retrospectivo, de caráter quantitativo, realizado com gestantes atendidas na maternidade do Hospital Regional do Sudoeste ­ PR, Francisco Beltrão. A amostra foi constituída por 216 gestantes, cujos dados foram coletados dos prontuários das pacientes. Incluíram-se as gestantes atendidas e diagnosticadas com diabetes mellitus gestacional no período de 2020 e com pelo menos um exame de glicose em jejum ou um teste de tolerância oral à glicose para comprovação diagnóstica. Foram exclusas as gestantes dos anos de 2019 e 2021 e oito transferências. A amostra teve maior porcentual do Diabetes mellitus gestacional (90,7%), com prevalência na raça branca (69,9%), faixa etária de 15- 35 anos (68,5%). Ademais,65,7% realizaram controle com dieta e 32,4 % necessitaram realizar o uso de insulina e 51,9%delas eram obesas. A presente pesquisateve considerável relevância, pois permitiu obter perfil epidemiológico de gestantes diagnosticadas com diabetes mellitus, trazendo benefícios, como identificação precocemente da doença, de modo a evitar complicações para gestantes e bebês. PALAVRAS-CHAVE: Gestacional; Diabetes; Prevalência; Maternidade.

Gestational Diabetes Mellitus is defined as a disease characterized by high levels of blood glucose, which is diagnosed for the first time during pregnancy. It can cause several maternal and fetal complications, often requiring early hospitalization and advanced care. The aim of thestudy was to characterize the epidemiological profile of pregnant women with gestational diabetes mellitus seen at a reference service. This is a descriptive, documentary, retrospective, quantitative study, carried out with pregnant women attended at the maternity hospital of the Hospital Regional do Sudoeste - PR in the city of Francisco Beltrão. The sample consisted of216 pregnant women, and data were collected from the patients' medical records. The study included all pregnant women who were attended and diagnosed with GDM in the period described, and who had at least one fasting glucose test or an oral glucose tolerance test for diagnostic confirmation. All pregnant women from the year 2019 and 2021 were excluded fromthe study. The sample had a higher percentage of GDM 90.7% according to race 69.9% werewhite, aged 15-35 years 68 , 5%, while 65.7% performed control with diet and 32.4% neededto use insulin and 51.9% of them were obese. This research had great results because it had an epidemiological profile of pregnant women diagnosed with Diabetes Mellitus, bringing benefitsand thus being able to identify gestational Diabetes mellitus early, aiming to avoid complications for the pregnant woman and the baby.

La diabetes mellitus gestacional se define como una enfermedad caracterizada por niveles elevados de glucosa en sangre, diagnosticada durante el embarazo. Esta enfermedad puede dar lugar a varias complicaciones maternas y fetales, que a menudo requieren una hospitalización temprana y cuidados avanzados. El objetivo es caracterizar el perfil epidemiológico de las gestantes con diabetes mellitus atendidas en el servicio de referencia. Se trata de un estudio descriptivo, documental, retrospectivo, de carácter cuantitativo, realizado con gestantes atendidas en la maternidad del Hospital Regional del Sudoeste - PR, Francisco Beltrão. La muestra estaba formada por 216 mujeres embarazadas, cuyos datos se recogieron de las historias clínicas de las pacientes. Se incluyeron las mujeres embarazadas atendidas y diagnosticadas de diabetes mellitus gestacional en el periodo 2020 y con al menos una prueba de glucosa en ayunas o una prueba de tolerancia oral a la glucosa para su diagnóstico. Se excluyeron las embarazadas de los años 2019 y 2021 y ocho traslados. La muestra tuvo un mayor porcentaje de Diabetes mellitus gestacional (90,7%), con prevalencia en la raza blanca (69,9%), grupo de edad 15-35 años (68,5%). Además, el 65,7% se controlaba con la dieta y el 32,4% necesitaba utilizar insulina y el 51,9% era obeso. La presente investigación tiene una relevancia considerable, ya que permite obtener el perfil epidemiológico de las gestantes diagnosticadas con diabetes mellitus, lo que conlleva beneficios, como la identificación precoz de la enfermedad, a fin de evitar complicaciones para las gestantes y los bebés.

Improvement of beta-cell function in conjunction with glycemic control after medical nutrition therapy in newly-diagnosed type 2 diabetes mellitus.

BACKGROUND: The current study aimed to reveal the correlation of beta-cell function and insulin sensitivity with glycemic control and weight control before and after medical nutrition therapy (MNT) in patients with newly-diagnosed type 2 diabetes mellitus. METHODS: We retrospectively analyzed consecutive 68 patients with newly-diagnosed type 2 diabetes mellitus who started MNT without antihyperglycemic medications and underwent a 75-g oral glucose tolerance test (OGTT) before and after the therapy. Beta-cell function was evaluated by the OGTT-derived disposition index, whereas insulin sensitivity was evaluated by Matsuda's insulin sensitivity index. RESULTS: After 4.0 ± 1.5 months of MNT, mean HbA1c and body mass index significantly decreased from 9.6 ± 1.8% to 7.2 ± 1.0% and from 26.9 ± 4.1 to 25.4 ± 3.7 kg/m2 (both P < 0.001), while the median disposition index and Matsuda's index significantly increased from 0.34 (0.20-0.68) to 0.88 (0.53-1.52) (P < 0.001) and from 4.70 (2.95-5.93) to 5.17 (3.48-6.89) (P = 0.003), respectively. The disposition index was significantly correlated with HbA1c levels both before and after MNT (r = -0.61 and -0.68; both P < 0.001). The magnitude of the correlation after MNT was not different from that before MNT (P = 0.42). Matsuda's index was correlated not with HbA1c levels but with body mass index, both before (r = 0.07 [P = 0.57] and r = -0.58 [P < 0.001]) and after MNT (r = -0.01 [P = 0.95] and r = -0.52 [P < 0.001]). CONCLUSIONS: Beta-cell function was improved in conjunction with glycemic control after MNT in patients with newly-diagnosed type 2 diabetes mellitus. Insulin sensitivity was linked with weight control rather than glycemic control.

Impact of food processing on postprandial glycaemic and appetite responses in healthy adults: a randomized, controlled trial.

Chickpeas are among the lowest glycaemic index carbohydrate foods eliciting protracted digestion and enhanced satiety responses. In vitro studies suggest that mechanical processing of chickpeas significantly increases starch digestion. However, there is little evidence regarding the impact of processing on postprandial glycaemic response in response to chickpea intake in vivo. Therefore, the aim of this study was to determine the effect of mechanical processing on postprandial interstitial glycaemic and satiety responses in humans. In a randomised crossover design, thirteen normoglycaemic adults attended 4 separate laboratory visits following an overnight fast. On each occasion, one of four test meals, matched for available carbohydrate content and consisting of different physical forms of chickpeas (whole, puree, and pasta) or control (mashed potato), was administered followed by a subsequent standardised lunch meal. Continuous glucose monitoring captured interstitial glucose responses, accompanied by periodic venous blood samples for retrospective analysis of C-peptide, glucagon like peptide-1 (GLP-1), ghrelin, leptin, resistin, and cortisol. Subjective appetite responses were measured by Visual Analogue Scale (VAS). Postprandial glycaemic responses were comparable between chickpea treatments albeit significantly lower than the control (p < 0.001). Similarly, all chickpea treatments elicited significantly lower C-peptide and GLP-1 responses compared to the control (p < 0.05), accompanied by enhanced subjective satiety responses (p < 0.05), whilst no significant differences in satiety hormones were detected among different intervention groups (p > 0.05). Chickpea consumption elicits low postprandial glycaemic responses and enhanced subjective satiety responses irrespective of processing methods.

Changes in blood glucose and lactate concentrations with hemodialysis.

INTRODUCTION: Blood glucose concentrations are recognized to vary during hemodialysis (HD), with hypoglycemia reported with glucose-free dialysates. As glucose can be converted to lactate, and conversely lactate to glucose, we wished to study factors associated with peri-dialytic changes in blood glucose. METHODS: We prospectively collected data including patient profile, dialysis prescription, hemodynamic parameters, medications, dialysis adequacy and monthly blood tests for three consecutive months. All patients used a 100 mg/dl glucose dialysate. Linear mixed model, general estimated equation and binary logistic regression were used for analysis. RESULTS: We studied 157 sessions in 55 patients, median age 67.1 (58.5-72.6) years, 67% male, 71% diabetic, 40% prescribed insulin, dialysis vintage 20.4 (10.7-57.7) months. Mean single pool Kt/Vurea and normalized protein nitrogen appearance rate (nPNA) were 1.70 ± 0.34 and 1.01 ± 0.30 g/kg/day respectively. Hypoglycemia (<70 mg/dl) occurred during 10 sessions (6.4%). 25% of non-diabetes experienced hypoglycemia. The % change in peri-dialytic blood glucose was associated with the % change in lactate (estimate of fixed effect = 0.23 p < 0.001) and pre-HD glucose (estimate of fixed effect = 0.09, p < 0.001). The fall in glucose was not associated with urea clearance, consumption of food, administration of insulin or antidiabetic medications, nPNA, body mass index, or pyridoxine concentrations. CONCLUSIONS: Peri-dialytic hypoglycemia cannot simply be explained by dialyzer clearance, as the corresponding fall in lactate would potentially suggest increased gluconeogenesis. Despite using a glucose containing dialysate, asymptomatic hypoglycemia occurred in 6.4% of sessions, suggesting a role for peri-dialytic blood glucose monitoring and avoiding fasting during dialysis.

High Fasting Glycemia Predicts Impairment of Cardiac Autonomic Control in Adults With Type 2 Diabetes: A Case-Control Study.

Introduction: Type 2 diabetes (T2D) is characterized by a metabolic disorder that elevates blood glucose concentration. Chronic hyperglycemia has been associated with several complications in patients with T2D, one of which is cardiac autonomic dysfunction that can be assessed from heart rate variability (HRV) and heart rate recovery (HRR) response, both associated with many aspects of health and fitness, including severe cardiovascular outcomes. Objective: To evaluate the effects of T2D on cardiac autonomic modulation by means of HRV and HRR measurements. Materials and Methods: This study has an observational with case-control characteristic and involved ninety-three middle-aged adults stratified into two groups (control group - CG, n = 34; diabetes group - DG, n = 59). After signing the free and informed consent form, the patients were submitted to the evaluation protocols, performed biochemical tests to confirm the diagnosis of T2D, collection of R-R intervals for HRV analysis and cardiopulmonary effort test to quantify HRR. Results: At rest, the DG showed a reduction in global HRV (SDNN= 19.31 ± 11.72 vs CG 43.09 ± 12.74, p < 0.0001), lower parasympathetic modulation (RMSSD= 20.49 ± 14.68 vs 52.41 ± 19.50, PNN50 = 4.76 ± 10.53 vs 31.24 ± 19.24, 2VD%= 19.97 ± 10.30 vs 28.81 ± 9.77, p < 0.0001 for both indices) and higher HRrest when compared to CG. After interruption of physical exercise, a slowed heart rate response was observed in the DG when compared to the CG. Finally, a simple linear regression showed that fasting glycemia was able to predict cardiac autonomic involvement in volunteers with T2D. Conclusion: Patients with T2D presented lower parasympathetic modulation at rest and slowed HRR after physical exercise, which may be associated with higher cardiovascular risks. The findings show the glycemic profile as an important predictor of impaired cardiac autonomic modulation.

Substantial Intra-Individual Variability in Post-Prandial Time to Peak in Controlled and Free-Living Conditions in Children with Type 1 Diabetes.

The optimal time to bolus insulin for meals is challenging for children and adolescents with type 1 diabetes (T1D). Current guidelines to control glucose excursions do not account for individual differences in glycaemic responses to meals. This study aimed to examine the within- and between-person variability in time to peak (TTP) glycaemic responses after consuming meals under controlled and free-living conditions. Participants aged 8-15 years with T1D ≥ 1 year and using a continuous glucose monitor (CGM) were recruited. Participants consumed a standardised breakfast for six controlled days and maintained their usual daily routine for 14 free-living days. CGM traces were collected after eating. Linear mixed models were used to identify within- and between-person variability in the TTP after each of the controlled breakfasts, free-living breakfasts (FLB), and free-living dinners (FLD) conditions. Thirty participants completed the study (16 females; mean age and standard deviation (SD) 10.5 (1.9)). The TTP variability was greater within a person than the variability between people for all three meal types (between-person vs. within-person SD; controlled breakfast 18.5 vs. 38.9 min; FLB 14.1 vs. 49.6 min; FLD 5.7 vs. 64.5 min). For the first time, the study showed that within-person variability in TTP glycaemic responses is even greater than between-person variability.

The impact of oral carbohydrate-rich supplement taken two hours before caesarean delivery on maternal and neonatal perioperative outcomes -- a randomized clinical trial.

BACKGROUND: To evaluate the impact of oral carbohydrate-rich (Ch-R) supplement taken 2 hours before an elective caesarean delivery (CD) on maternal and neonatal perioperative outcomes. METHODS: Ninety pregnant women undergoing elective CD were randomized into the Ch-R group, placebo group and fasting group equally. Participants' blood was drawn at three time points, before intervention, immediately after and 1 day after the surgery to measure maternal and neonatal biochemical indices. Meanwhile women's perioperative symptoms and signs were recorded. RESULTS: Eighty-eight pregnant women were finally included in the study. Women who had drunk Ch-R supplement had lower postoperative insulin level (ß = - 3.50, 95% CI - 5.45 to - 1.56), as well as postoperative HOMA-IR index (ß = - 0.74, 95% CI - 1.15 to - 0.34), compared with women who had fasted. Additionally, neonates of mothers who were allocated in the Ch-R group also had a higher glucose level, compared with neonates of mothers in the fasting group (ß = 0.40, CI 0.17 to 0.62). CONCLUSION: Oral Ch-R solution administered 2 hours before an elective CD may not only alleviate maternal postoperative insulin resistance, but also comfort women's preoperative thirst and hunger, compared to fasting. Additionally, it may increase neonatal glucose level as well. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000033163 . Data of Registration: 2020-5-22.

[Euglycemic ketoacidosis - rare condition on the rise]. / Euglykäme Ketoazidose ­ ein Kolibri, der zur Taube werden könnte.

SGLT2 inhibitors have been developed as antidiabetics. Large randomized prospective studies have shown prognostic benefit in patients with heart and/or renal insufficiency regarding cardiovascular and general endpoints - even in absence of type 2 diabetes mellitus. This extends the indication to large groups of multimorbid patients. SGLT2 inhibitors induce ketogenesis comparable to fasting conditions. This may - in presence of additional catabolic factors - deteriorate into life-threatening ketoacidosis - probably due to increased reabsorption of ketone bodies from urine as well as the blockage of SGLT2 receptors on α-cells of the pancreas. Euglycaemic ketoacidosis (eKA) under SGLT2 inhibition occurs in about 2:1000 years of treatment. The diagnosis is challenging: in eKA, blood sugar levels are often normal, and ketone detection in urinalysis can be falsely negative, while glucosuria is excessive compared to euglycemic blood-glucose. The management corresponds to classical diabetic ketoacidosis, but special features of blood glucose target, hydration and potassium management should be considered. SGLT2 inhibitors should be paused if a longer fasting period is expected ("sick-day-break"). Due to the soaring number of prescriptions, a significant increase in the prevalence of eKA is expected. Immediate diagnosis and therapy are essential in emergency and intensive care medicine.

Longitudinal Glycaemic Profiles during Remission in 6q24-Related Transient Neonatal Diabetes Mellitus.

INTRODUCTION: Transient neonatal diabetes mellitus (TNDM) is a rare condition that is characterized by the presence of diabetes mellitus during the first 6 months of life and remission by 18 months of age. It usually relapses at a median age of 14 years. Hyperinsulinaemic hypoglycaemia is a relatively common complication during remission. Although ß-cell function is reported to be impaired at relapse, the clinical course of glycaemic profiles during remission in patients with TNDM remains largely unknown. CASE PRESENTATION: Longitudinal glycaemic profiles were investigated annually from remission (185 days) to relapse (14.5 years) in a patient with TNDM due to paternal 6q24 duplication using the oral glucose tolerance test (glucose intake: 1.75 g/kg to a maximum of 75 g). The patient's ß-cell function and insulin sensitivity were assessed by calculating the insulinogenic index, homeostasis model assessment of ß-cell function (HOMA-ß), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index, and Matsuda index. Early insulin response to glucose intake was impaired throughout remission, whereas fasting insulin and ß-cell function by HOMA-ß gradually increased in the first few years since remission, followed by a gradual decline in function. In contrast, HOMA-IR fluctuated and peaked at 6.5 years of age. CONCLUSION: This is the first report of annual longitudinal glycaemic profiles in a patient with 6q24-related TNDM during remission. We identified fluctuations in ß-cell function and insulin resistance during remission.

Ovarian insufficiency impairs glucose-stimulated insulin secretion through activation of hypothalamic de novo ceramide synthesis.

Oestrogens regulate body weight through their action on hypothalamus to modulate food intake and energy expenditure. Hypothalamic de novo ceramide synthesis plays a central role on obesity induced by oestrogen deficiency. Depletion in oestrogens is also known to be associated with glucose intolerance, which favours type 2 diabetes (T2D). However, the implication of hypothalamic ceramide in the regulation of glucose homeostasis by oestrogen is unknown. Here, we studied glucose homeostasis and insulin secretion in ovariectomized (OVX) female rats. OVX induces body weight gain associated with a hypothalamic inflammation and impaired glucose homeostasis. Genetic blockade of ceramide synthesis in the ventromedial nucleus of the hypothalamus (VMH) reverses hypothalamic inflammation and partly restored glucose tolerance induced by OVX. Furthermore, glucose-stimulated insulin secretion (GSIS) is increased in OVX rats due to a raise of insulin secretion second phase, a characteristic of early stage of T2D. In contrast, GSIS from isolated islets of OVX rats is totally blunted. Inhibition of ceramide synthesis in the VMH restores GSIS from isolated OVX islets and represses the second phase of insulin secretion. Stimulation of oestrogen receptor α (ERα) by oestradiol (E2) down-regulates ceramide synthesis in hypothalamic neuronal GT1-7 cells but no in microglial SIM-A9 cells. In contrast, genetic inactivation of ERα in VMH upregulates ceramide synthesis. These results indicate that hypothalamic neuronal de novo ceramide synthesis triggers the OVX-dependent impairment of glucose homeostasis which is partly mediated by a dysregulation of GSIS.

Convulsions in children hospitalized for acute gastroenteritis.

The study aim was to examine possible correlates of convulsions in children hospitalized for acute gastroenteritis (AGE). Data collected in a prospective study of AGE hospitalizations in children aged 0-59 months in 3 hospitals in Israel during 2008-2015 were analyzed. Stool samples were tested for rotavirus using immunochromatography and stool culture was performed for the detection of Salmonella, Shigella and Campylobacter We compared clinical and demographic characteristics of children hospitalized for AGE who had convulsions (n = 68, cases) with children hospitalized for AGE without convulsions (n = 3505, controls). Age differed between children with and without convulsions (p = 0.005); the former were mostly toddlers aged 12-23 months (51%) compared to 30% of the control group. A higher percentage of cases tested positive for Shigella (11% vs. 4%, p = 0.002), the opposite was found for rotavirus (2% vs. 30% p < 0.001). A multivariable model showed that body temperature (OR 2.91 [95% CI 1.78-4.76], p < 0.001) and high blood glucose level (> 120 mg/dL) (OR 5.71 [95% CI 1.27-25.58] p = 0.023) were positively related to convulsions in children with AGE, while severe AGE (Vesikari score ≥ 11) was inversely related with convulsions (OR 0.09 [95% CI 0.03-0.24], p < 0.001). Conclusion: Elevated body temperature is associated with convulsions in children with AGE, but not severity of AGE, while hyperglycemia might reflect a neuroendocrine stress reaction to convulsions, AGE or both.

Effects of Soy Isoflavones on Glycemic Control and Lipid Profile in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The aim of the report was to investigate the impact of soy protein and isoflavones on glucose homeostasis and lipid profile in type 2 diabetes. The studies used in this report were identified by searching through the MEDLINE and EMBASE databases (up to 2020). Meta-regression and subgroup analyses were performed to explore the influence of covariates on net glycemic control and lipid changes. Weighted mean differences and 95% confidence intervals (CI) were calculated by using random-effect models. Changes in the lipid profile showed statistically significant decreases in total cholesterol and LDL-C concentrations: ‒0.21 mmol/L; 95% CI, ‒0.33 to ‒0.09; p = 0.0008 and ‒0.20 mmol/L; 95% CI, ‒0.28 to ‒0.12; p < 0.0001, respectively, as well as in HDL-C (-0.02 mmol/L; 95% CI, -0.05 to 0.01; p = 0.2008 and triacylglycerols (-0.19 mmol/L; 95% CI, -0.48 to 0.09; p = 0.1884). At the same time, a meta-analysis of the included studies revealed statistically insignificant reduction in fasting glucose, insulin, HbA1c, and HOMA-IR (changes in glucose metabolism) after consumption of soy isoflavones. The observed ability of both extracted isoflavone and soy protein with isoflavones to modulate the lipid profile suggests benefits in preventing cardiovascular events in diabetic subjects. Further multicenter studies based on larger and longer duration studies are necessary to determine their beneficial effect on glucose and lipid metabolism.

Molecular mechanisms from insulin-mimetic effect of vitamin D: treatment alternative in Type 2 diabetes mellitus.

Diabetes mellitus is a complex and multifactorial disease with a global prevalence that exceeds 425 million people. Type 2 diabetes mellitus (T2DM) is characterized by a state of insulin resistance, which leads to metabolic alterations that aggravate the state of health of people. Vitamin D deficiency appears to play an important role in the triggering mechanisms of insulin resistance. In this review, an analysis is made of the biochemical mechanisms associated with the insulin-mimetic effect of vitamin D, its supplementation being a possible nutritional strategy for the T2DM treatment. The current scientific evidence is extensive regarding the dose of vitamin D used for an insulin-mimetic effect. However, clinical trials and systematic reviews show statistical differences on glucose, insulin, and glycated hemoglobin levels of patients with T2DM, associated with activation mechanisms of transcription factors related to genes of the glucide metabolism and the insulin receptor, and the regulation of intracellular Ca2+ insulin concentrations. Likewise, an indirect mechanism associated with antioxidant and anti-inflammatory effects has been shown that also leads to sensitivity to the insulin receptor. The use of a specific dose of vitamin D could be an effective alternative in the T2DM treatment, which would reduce the risk of complications derived from hyperglycemia.

Hyperinsulinemic Compensation for Insulin Resistance Occurs Independent of Elevated Glycemia in Male Dogs.

Insulin resistance engenders a compensatory increase in plasma insulin. Inadequate compensation is a primary element in the pathogenesis of type 2 diabetes. The signal that heralds developing insulin resistance and initiates hyperinsulinemic compensation is not known. It has often been assumed to be increased glucose. We tested this assumption by determining whether development of fasting and/or glucose-stimulated hyperinsulinemia with diet-induced insulin resistance occurs because of concomitant elevation of glycemia. Male dogs (n = 58) were fed a hypercaloric, fat-supplemented diet for 6 weeks. Dogs underwent magnetic resonance imaging to quantify total and regional (visceral, subcutaneous) adiposity as well as euglycemic hyperinsulinemic clamps. A subset of animals also underwent an insulin-modified intravenous glucose tolerance test to assess insulin sensitivity, acute insulin response (AIRg), and glucose effectiveness. Fat feeding caused modest weight gain, increased visceral and subcutaneous fat, and insulin resistance at both peripheral and hepatic levels. Hyperinsulinemic compensation was observed in fasting levels as well as increased AIRg. However, we observed absolutely no increase in carefully measured fasting, evening (6 to 8 pm) or nocturnal glycemia (2 to 4 am). Insulin resistance and hyperinsulinemia occurred despite no elevation in 24-hour glucose. Compensatory development of hyperinsulinemia during diet-induced insulin resistance occurs without elevated fasting or 24-hour glycemia. These data refute the idea that glucose itself is a requisite signal for ß-cell upregulation. Alternative feedback mechanisms need to be identified.

Altered adipokines in obese adolescents: a cross-sectional and longitudinal analysis across the spectrum of glycemia.

Obesity and type 2 diabetes are rapidly increasing in the adolescent population. We sought to determine whether adipokines, specifically leptin, C1q/TNF-related proteins 1 (CTRP1) and CTRP9, and the hepatokine fibroblast growth factor 21 (FGF21), are associated with obesity and hyperglycemia in a cohort of lean and obese adolescents, across the spectrum of glycemia. In an observational, longitudinal study of lean and obese adolescents, we measured fasting laboratory tests, oral glucose tolerance tests, and adipokines including leptin, CTRP1, CTRP9, and FGF21. Participants completed baseline and 2-year follow-up study visits and were categorized as lean (LC, lean control; n = 30), obese normoglycemic (ONG; n = 61), and obese hyperglycemic (OHG; n = 31) adolescents at baseline and lean (n = 8), ONG (n = 18), and OHG (n = 4) at follow-up. Groups were compared using ANOVA and regression analysis, and linear mixed effects modeling was used to test for differences in adipokine levels across baseline and follow-up visits. Results showed that at baseline, leptin was higher in all obese groups (P < 0.001) compared with LC. FGF21 was higher in OHG participants compared with LC (P < 0.001) and ONG (P < 0.001) and positively associated with fasting glucose (P < 0.001), fasting insulin (P < 0.001), Homeostasis Model Assessment-Insulin Resistance Index (HOMA-IR; P < 0.001), and hemoglobin A1c (HbA1c; P = 0.01). CTRP1 was higher in OHG compared with ONG (P = 0.03). CTRP9 was not associated with obesity or hyperglycemia in this pediatric cohort. At 2 years, leptin decreased in ONG (P = 0.003) and FGF21 increased in OHG (P = 0.02), relative to lean controls. Altered adipokine levels are associated with the inflammatory milieu in obese youth with and without hyperglycemia. In adolescence, the novel adipokine CTRP1 was elevated with hyperglycemia, whereas CTRP9 was unchanged in this cohort.NEW & NOTEWORTHY Leptin is higher in obese adolescents and FGF21 is higher in obese hyperglycemic adolescents. The novel adipokine CTRP1 is higher in obese hyperglycemic adolescents, whereas CTRP9 was unchanged in this adolescent cohort.

Significant abnormal glycemic variability increased the risk for arrhythmias in elderly type 2 diabetic patients.

BACKGROUND: Little is known about whether the influence of glycemic variability on arrhythmia is related to age in type 2 diabetes mellitus (T2DM). Therefore, we aimed to compare the association between glycemic variability and arrhythmia in middle-aged and elderly T2DM patients. METHODS: A total of 107 patients were divided into two groups: elderly diabetes mellitus group (EDM, n = 73) and middle-aged diabetes mellitus group (MDM, n = 34). The main clinical data, continuous glucose monitoring (CGM) and dynamic ECG reports were collected. The parameters including standard deviation of blood glucose (SDBG), largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE), absolute means of daily differences (MODD), time in range (TIR), time below range (TBR), time above range (TAR), coefficient of variation (CV) were tested for glycemic variability evaluation. RESULTS: In terms of blood glucose fluctuations, MAGE (5.77 ± 2.16 mmol/L vs 4.63 ± 1.89 mmol/L, P = 0.026), SDBG (2.39 ± 1.00 mmol/L vs 2.00 ± 0.82 mmol/L, P = 0.048), LAGE (9.53 ± 3.37 mmol/L vs 7.84 ± 2.64 mmol/L, P = 0.011) was significantly higher in EDM group than those of MDM group. The incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat were significantly higher in EDM group compared with the MDM group (all P < 0.05). Among patients with hypoglycemia events, the incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat (all P < 0.05) were significantly higher in the EDM group than those in the MDM group. In EDM group, TIR was negatively correlated with atrial tachycardia in the MAGE1 layer and with atrial tachycardia and ventricular premature beat in the MAGE2 layer, TBR was significantly positively correlated with atrial tachycardia in the MAGE2 layer (all P < 0.05). In MDM group, TAR was positively correlated with ventricular premature beat and atrial tachycardia in the MAGE2 layer (all P < 0.05). CONCLUSIONS: The study demonstrated the elderly patients had greater glycemic variability and were more prone to arrhythmias. Therefore, active control of blood glucose fluctuation in elderly patients will help to reduce the risk of severe arrhythmia.

The Role of Incretins on Insulin Function and Glucose Homeostasis.

The incretin effect-the amplification of insulin secretion after oral vs intravenous administration of glucose as a mean to improve glucose tolerance-was suspected even before insulin was discovered, and today we know that the effect is due to the secretion of 2 insulinotropic peptides, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). But how important is it? Physiological experiments have shown that, because of the incretin effect, we can ingest increasing amounts of amounts of glucose (carbohydrates) without increasing postprandial glucose excursions, which otherwise might have severe consequences. The mechanism behind this is incretin-stimulated insulin secretion. The availability of antagonists for GLP-1 and most recently also for GIP has made it possible to directly estimate the individual contributions to postprandial insulin secretion of a) glucose itself: 26%; b) GIP: 45%; and c) GLP-1: 29%. Thus, in healthy individuals, GIP is the champion. When the action of both incretins is prevented, glucose tolerance is pathologically impaired. Thus, after 100 years of research, we now know that insulinotropic hormones from the gut are indispensable for normal glucose tolerance. The loss of the incretin effect in type 2 diabetes, therefore, contributes greatly to the impaired postprandial glucose control.