Improved meal-related insulin processing contributes to the enhancement of B-cell function by the DPP-4 inhibitor vildagliptin in patients with type 2 diabetes.

The aim of this study was to evaluate the contribution of insulin processing to the improved meal-related B-cell function previously shown with the DPP-4 inhibitor vildagliptin. Fifty-five patients with type 2 diabetes (56.5+/-1.5 years; BMI=29.6+/-0.5 kg/m(2); FPG=9.9+/-0.2 mmol/l; HbA1c=7.7+/-0.1 %) were studied: 29 patients were treated with vildagliptin and 26 patients with placebo, both added to an ongoing metformin regimen (1.5-3.0 g/day). A standardized breakfast was given at baseline and after 52 weeks of treatment, and proinsulin related to insulin secretion was measured with C-peptide in the fasting and postprandial (over 4 h post-meal) states to evaluate B-cell function. The between-treatment difference (vildagliptin-placebo) in mean change from baseline in fasting proinsulin to C-peptide ratio (fastP/C) was -0.007+/-0.009 (p=0.052). Following the standard breakfast, 52 weeks of treatment with vildagliptin significantly decreased the dynamic proinsulin to C-peptide ratio (dynP/C) relative to placebo by 0.010+/-0.008 (p=0.037). Importantly, when the P/C was expressed in relation to the glucose stimulus (i.e., the fasting glucose and glucose AUC(0-240 min), respectively), the P/C relative to glucose was significantly reduced with vildagliptin vs. placebo, both in the fasting state (p=0.023) and postprandially (p=0.004). In conclusion, a more efficient B-cell insulin processing provides further evidence that vildagliptin treatment ameliorates abnormal B-cell function in patients with type 2 diabetes.     

Novel heterocyclic DPP-4 inhibitors for the treatment of type 2 diabetes

Novel deazaxanthine-based DPP-4 inhibitors have been identified that are potent (IC(50) <10nM) and highly selective versus other dipeptidyl peptidases. Their synthesis and SAR are reported, along with initial efforts to improve the PK profile through decoration of the deazaxanthine core. Optimisation of compound 3a resulted in the identification of compound (S)-4i, which displayed an improved in vitro and ADME profile. Further enhancements to the PK profile were possible by changing from the deazahypoxanthine to the deazaxanthine template, culminating in compound 12g, which displayed good ex vivo DPP-4 inhibition and a superior PK profile in rat, suggestive of once daily dosing in man.     

GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone with antidiabetic action through its ability to stimulate insulin secretion, increase beta cell neogenesis, inhibit beta cell apoptosis, inhibit glucagon secretion, delay gastric emptying and induce satiety. It has therefore been explored as a novel treatment of type 2 diabetes. A problem is, however, that GLP-1 is rapidly inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme, which results in a short circulating half-life of the active form of GLP-1 (< 2 min). Two strategies have been employed to overcome this obstacle as a treatment of diabetes. One is to use GLP-1 receptor agonists that have a prolonged half-life due to reduced degradation by DPP-4. These GLP-1 mimetics include exenatide and liraglutide. Another strategy is to inhibit the enzyme DPP-4, which prolongs the half-life of endogenously released active GLP-1. Both these strategies have been successful in animal studies and in clinical studies of up to one year's treatment. This review will summarize the background and the current (mid 2004) clinical experience with these two strategies.     

Glucagon-like peptide 1 improved glycemic control in type 1 diabetes

BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its agonists are under assessment in treatment of type 2 diabetes, by virtue of their antidiabetic actions, which include stimulation of insulin secretion, inhibition of glucagon release, and delay of gastric emptying. We examined the potential of GLP-1 to improve glycemic control in type 1 diabetes with no endogenous insulin secretion. METHODS: Dose-finding studies were carried out to establish mid range doses for delay of gastric emptying indicated by postponement of pancreatic polypeptide responses after meals. The selected dose of 0.63 micrograms/kg GLP-1 was administered before breakfast and lunch in 8-hour studies in hospital to establish the efficacy and safety of GLP-1. In outside-hospital studies, GLP-1 or vehicle was self-administered double-blind before meals with usual insulin for five consecutive days by five males and three females with well-controlled C-peptide-negative type 1 diabetes. Capillary blood glucose values were self-monitored before meals, at 30 and 60 min after breakfast and supper, and at bedtime. Breakfast tests with GLP-1 were conducted on the day before and on the day after 5-day studies. Paired t-tests and ANOVA were used for statistical analysis. RESULTS: In 8-hour studies time-averaged incremental (delta) areas under the curves(AUC) for plasma glucose through 8 hours were decreased by GLP-1 compared to vehicle (3.2 PlusMinus; 0.9, mean PlusMinus; se, vs 5.4 PlusMinus; 0.8 mmol/l, p <.05), and for pancreatic polypeptide, an indicator of gastric emptying, through 30 min after meals (4.0 PlusMinus; 3.1 vs 37 PlusMinus; 9.6 pmol/l, p <.05) with no adverse effects. Incremental glucagon levels through 60 min after meals were depressed by GLP-1 compared to vehicle (-3.7 PlusMinus; 2.5 vs 3.1 PlusMinus; 1.9 ng/l, p <.04). In 5-day studies, AUC for capillary blood glucose levels were lower with GLP-1 than with vehicle (-0.64 PlusMinus; 0.33 vs 0.34 PlusMinus; 0.26 mmol/l, p <.05). No assisted episode of hypoglycaemia or change in insulin dosage occurred. Breakfast tests on the days immediately before and after 5-day trials showed no change in the effects of GLP-1. CONCLUSION: We have demonstrated that subcutaneous GLP-1 can improve glucose control in type 1 diabetes without adverse effects when self-administered before meals with usual insulin during established intensive insulin treatment programs.     

Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control

Patients with type 2 diabetes are at a high risk for acute cardiovascular events, which usually arise from the rupture of a vulnerable coronary lesion characterized by specific morphological plaque features. Thus, the identification of vulnerable plaques is of utmost clinical importance in patients with type 2 diabetes. However, there is currently no scoring system available to identify vulnerable lesions based on plaque characteristics. Thus, we aimed to characterize the diagnostic value of optical coherence tomography (OCT) - derived lesion characteristics to quantify plaque vulnerability both as individual parameters and when combined to a score in patients with type 2 diabetes. OCT was performed in the coronary culprit lesions of 112 patients with type 2 diabetes. The score, which quantifies plaque vulnerability, was defined as the predicted probability that a lesion is the cause for an acute coronary syndrome (ACS) (vs. stable angina (SAP)) based on its specific plaque morphology. Multivariable logistic regression analysis demonstrated that plaque vulnerability was independently predicted by the minimal fibrous cap thickness overlying a lesion’s lipid core (odds ratio (OR) per 10 μm 0.478, p = 0.002), the medium lipid arc (OR per 90° 13.997, p < 0.001), the presence of macrophages (OR 4.797, p = 0.015) and the lipid plaque length (OR 1.290, p = 0.098). Receiver-operating-characteristics (ROC) analyses demonstrated that these parameters combined to a score demonstrate an excellent diagnostic efficiency to identify culprit lesions of patients with ACS (vs. SAP, AUC 0.90, 95% CI 0.84-0.96). This is the first study to present a score to quantify lesion vulnerability in patients with type 2 diabetes. This score may be a valuable adjunct in decision-making and useful in guiding coronary interventions.     

Antioxidant alpha-tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes

We have shown recently that oxidative stress by chronic hyperglycemia damages the pancreatic beta-cells of GK rats, a model of non-obese type 2 diabetes, which may worsen diabetic condition and suggested the administration of antioxidants as a supportive therapy. To determine if natural antioxidant alpha-tocopherol (vitamin E) has beneficial effects on the glycemic control of type 2 diabetes, GK rats were fed a diet containing 0, 20 or 500 mg/kg diet alpha-tocopherol. Intraperitoneal glucose tolerance test revealed a significant increment of insulin secretion at 30 min and a significant decrement of blood glucose levels at 30 and 120 min after glucose loading in the GK rats fed with high alpha-tocopherol diet. The levels of glycated hemoglobin A1c, an indicator of glycemic control, were also reduced. Vitamin E supplementation clearly ameliorated diabetic control of GK rats, suggesting the importance of not only dietary supplementation of natural antioxidants but also other antioxidative intervention as a supportive therapy of type 2 diabetic patients.     

Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes

Exenatide (synthetic exendin-4), glucagon-like peptide-1 (GLP-1), and GLP-1 analogues have actions with the potential to significantly improve glycemic control in patients with diabetes. Evidence suggests that these agents use a combination of mechanisms which may include glucose-dependent stimulation of insulin secretion, suppression of glucagon secretion, enhancement of beta-cell mass, slowing of gastric emptying, inhibition of food intake, and modulation of glucose trafficking in peripheral tissues. The short in vivo half-life of GLP-1 has proven a significant barrier to continued clinical development, and the focus of current clinical studies has shifted to agents with longer and more potent in vivo activity. This review examines recent exendin-4 pharmacology in the context of several known mechanisms of action, and contrasts exendin-4 actions with those of GLP-1 and a GLP-1 analogue. One of the most provocative areas of recent research is the finding that exendin-4 enhances beta-cell mass, thereby impeding or even reversing disease progression. Therefore, a major focus of this is article an examination of the data supporting the concept that exendin-4 and GLP-1 may increase beta-cell mass via stimulation of beta-cell neogenesis, stimulation of beta-cell proliferation, and suppression of beta-cell apoptosis.     

A randomized,placebo-controlled clinical trial evaluating the safety and efficacy of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus inadequately controlled by glimepiride and metformin

Background

Type 2 diabetes (T2D) is a progressive disease that often requires a patient to use multiple antihyperglycemic agents to achieve glycemic control with disease progression. Omarigliptin is a once-weekly dipeptidyl peptidase-4 inhibitor. The purpose of this trial was to assess the efficacy and safety of adding omarigliptin to the treatment regimen of patients with T2D inadequately controlled by dual therapy with metformin and glimepiride.

Methods

Patients with T2D and HbA1c ≥7.5% and ≤10.5% while on metformin (≥1500 mg/day) and glimepiride (≥4 mg/day) were randomized to omarigliptin 25 mg once-weekly (N = 154) or placebo (N = 153) for 24 weeks. The primary objective was to assess whether omarigliptin was superior to placebo in reducing HbA1c at Week 24. Secondary objectives were to assess the effects of omarigliptin vs. placebo on FPG and the proportion of subjects attaining HbA1c goals of <7% and <6.5%.

Results

From a mean baseline HbA1c of 8.5% (omarigliptin) and 8.6% (placebo), the least squares (LS) mean change from baseline in HbA1c at Week 24 was ?0.67% in the omarigliptin group and ?0.06% in the placebo group, with a between-group difference (95% CI) of ?0.61% (?0.85, ?0.38). Treatment with omarigliptin resulted in a significantly greater reduction in FPG relative to placebo (LS mean difference [95% CI] -0.9 mmol/L [?1.4, ?0.4]; p < 0.001). The proportion of patients achieving glycemic goals of <7.0% and <6.5% was higher in the omarigliptin group relative to the placebo group. The overall incidences of adverse events (AEs), serious AEs, drug-related AEs and discontinuations were generally similar between treatment groups. The incidence of symptomatic hypoglycemia was 10.5% in the omarigliptin group and 8.5% in the placebo group. Relative to baseline, omarigliptin and placebo treatments were associated with LS mean changes in body weight of ?0.1 kg and ?0.9 kg, respectively.

Conclusion

In patients with T2D and inadequate glycemic control on dual therapy with metformin and glimepiride, compared with placebo, once-weekly omarigliptin provided greater improvement in glycemic control and was generally well tolerated.

Trial registration

ClinicalTrials.gov: NCT01704261, EudraCT Number: 2012-002612-10. Trial Registration Date: October 8, 2012.

     

强化控糖后加用盐酸吡格列酮治疗2型糖尿病的临床疗效观察

目的观察强化控糖后加用盐酸吡格列酮治疗2型糖尿病的临床疗效。方法 60例使用口服降糖药物治疗的血糖控制不佳的2型糖尿病患者,入院后先进行胰岛素泵强化控糖治疗,患者血糖达到目标值后（FPG〈7.0 mmol/L,2 h PG〈10.0 mmol/L）,改为三餐前门冬胰岛素联合睡前甘精胰岛素继续强化治疗,1周后按1：1的比例随机分为两组,一组继续使用三餐前门冬胰岛素联合睡前甘精胰岛素治疗（对照组）,一组在三餐前门冬胰岛素联合睡前甘精胰岛素的基础上加用盐酸吡格列酮30 mg/日（治疗组）。1～4周我院住院治疗,5～12周门诊随访,若出现FPG及2 h PG明显下降或低血糖反应,则减少胰岛素用量。观察加用盐酸吡格列酮治疗前以及治疗12周时FPG、2 h PG、HbAlc、胰岛素用量、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、体重指数的变化情况。结果 （1）治疗组胰岛素用量明显下降,与加用盐酸吡格列酮治疗前有明显差异（P〈0.05）;对照组的胰岛素用量治疗前后无明显差异（P〉0.05）;（2）治疗组与对照组加用盐酸吡格列酮治疗前后FPG、2hPG均无明显差异（P〉0.05）。（3）治疗组HbAlc有所下降,与加用盐酸吡格列酮治疗前有明显差异（P〈0.05）,对照组HbAlc也有所下降,差异明显（P〈0.05）,但治疗后两组比较无明显差异（P〉0.05）。（4）加用盐酸吡格列酮后,治疗组TG下降,HDL-C升高,与同组治疗前相比,差异明显（P〈0.05）,对照组与治疗前相比差异不明显,组间比较差异有显著性（P〈0.05）。结论在强化控糖血糖达标后,加用盐酸吡格列酮继续治疗,可以明显降低患者胰岛素的使用剂量,提高患者的依从性,并且能改善血脂代谢紊乱,对于减少心血管并发症的发生有一定益处。     

Reproducibility of a glycemic response to mixed meals in type 2 diabetes mellitus.

OBJECTIVE: To evaluate the inter-patient and intra-patient reproducibility of the glycemic response to a mixed meal in individuals with type 2 diabetes mellitus (DM). SUBJECTS/SETTING: Six individuals with DM were admitted to the General Clinical Research Center for 6 days. INTERVENTION: Subjects consumed 3 different meal plans consisting of 4 meals daily (breakfast, lunch, dinner and snack) on 2 separate occasions. Serum insulin and glucose levels were sampled at 19 time points every day. The glycemic response (GR) to a meal was calculated as the area under the glucose response curve after consumption of a given meal. In addition, the incremental area under the curve (IGR) was calculated assuming a pre-prandial (baseline) glucose value before each meal as zero. RESULTS: Intra-patient correlation coefficients (R) of GR for meals in subjects with DM were quite good, ranging 0.69-0.94. The range of the inter-patient coefficients of variation (CV) for the same meals was 21.5-30.4%. For IGR, the R values ranged from 0.64 to 0.91 for 8 out of 12 meals, confirming good intra-patient reproducibility for these meals. CV for IGR ranged from 31% to 113%. CONCLUSIONS: For patients with DM, the GR of individual meals exhibits excellent intra-patient reproducibility, allowing prediction of the glycemic response to a given meal in an individual subject. However, significant inter-patient variability of the GR precludes its use for the prediction of post-prandial glucose concentrations in groups of patients with diabetes.     

Relation between psychosocial variables and the glycemic control of patients with type 2 diabetes: A cross-sectional and prospective study

Background  

This cross-sectional and prospective study used a variety of psychological inventories to evaluate the relationship between psychosocial factors and the glycemic control of patients with type 2 diabetes.     

Acute lowering of circulating fatty acids improves insulin secretion in a subset of type 2 diabetes subjects

We tested the effects of acute perturbations of elevated fatty acids (FA) on insulin secretion in type 2 diabetes. Twenty-one type 2 diabetes subjects with hypertriglyceridemia (triacylglycerol >2.2 mmol/l) and 10 age-matched nondiabetic subjects participated. Glucose-stimulated insulin secretion was monitored during hyperglycemic clamps for 120 min. An infusion of Intralipid and heparin was added during minutes 60-120. In one of two tests, the subjects ingested 250 mg of Acipimox 60 min before the hyperglycemic clamp. A third test (also with Acipimox) was performed in 17 of the diabetic subjects after 3 days of a low-fat diet. Acipimox lowered FA levels and enhanced insulin sensitivity in nondiabetic and diabetic subjects alike. Acipimox administration failed to affect insulin secretion rates in nondiabetic subjects and in the group of diabetic subjects as a whole. However, in the diabetic subjects, Acipimox increased integrated insulin secretion rates during minutes 60-120 in the 50% having the lowest levels of hemoglobin A(1c) (379 +/- 34 vs. 326 +/- 30 pmol x kg(-1) x min(-1) without Acipimox, P < 0.05). A 3-day dietary intervention diminished energy from fat from 39 to 23% without affecting FA levels and without improving the insulin response during clamps. Elevated FA levels may tonically inhibit stimulated insulin secretion in a subset of type 2 diabetic subjects.     

Trace elements,oxidative stress and glycemic control in young people with type 1 diabetes mellitus

Trace elements and oxidative stress are associated with glycemic control and diabetic complications in type 1 diabetes mellitus. In this study, we analyzed the levels of serum copper, zinc, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and urinary MDA and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in 33 type 1 diabetic patients with optimal and suboptimal glycemic control (HbA_1C < 9.0%) and 40 patients with poor glycemic control (HbA_1C ≥ 9%) and 27 age- and sex-matched non-diabetic controls to evaluate the differences between these markers in different glycemic control states. Diabetic patients, especially poor-glycemic-control subjects (HbA_1C ≥ 9%), exhibited significantly lower levels of serum zinc and increased levels of serum copper (and, therefore, increased serum copper-to-zinc ratios), serum SOD, blood MDA, and urinary MDA and 8-OHdG, relative to non-diabetic subjects. Furthermore, significant correlations existed in these patients between the serum copper, serum copper-to-zinc ratio, and urinary MDA (all p < 0.001) and the levels of urinary 8-OHdG (p = 0.007) and HbA_1C. Our results suggest that high serum copper levels and oxidative stress correlate with glycemic control. Therefore, strict glycemic control, decreased oxidative stress, and a lower copper concentration might prevent diabetic complications in patients with type 1 diabetes mellitus.     

Chronic administration of ezetimibe increases active glucagon-like peptide-1 and improves glycemic control and pancreatic beta cell mass in a rat model of type 2 diabetes

Ezetimibe is a cholesterol-lowering agent targeting Niemann-Pick C1-like 1, an intestinal cholesterol transporter. Inhibition of intestinal cholesterol absorption with ezetimibe may ameliorate several metabolic disorders including hepatic steatosis and insulin resistance. In this study, we investigated whether chronic ezetimibe treatment improves glycemic control and pancreatic beta cell mass, and alters levels of glucagon-like peptide-1 (GLP-1), an incretin hormone involved in glucose homeostasis. Male LETO and OLETF rats were treated with vehicle or ezetimibe (10 mg kg⁻¹ day⁻¹) for 20 weeks via stomach gavage. OLETF rats were diabetic with hyperglycemia and significant decreases in pancreatic size and beta cell mass compared with LETO lean controls. Chronic treatment of OLETF rats with ezetimibe improved glycemic control during oral glucose tolerance test compared with OLETF controls. Moreover, ezetimibe treatment rescued the reduced pancreatic size and beta cell mass in OLETF rats. Interestingly, ezetimibe significantly decreased serum dipeptidyl peptidase-4 activity and increased serum active GLP-1 in OLETF rats without altering serum total GLP-1. These findings demonstrated that chronic administration of ezetimibe improves glycemic control and pancreatic beta cell mass, and increases serum active GLP-1 levels, suggesting possible involvement of GLP-1 in the ezetimibe-mediated beneficial effects on glycemic control.     

Combined treatment with DPP-4 inhibitor linagliptin and SGLT2 inhibitor empagliflozin attenuates neointima formation after vascular injury in diabetic mice

Incretin therapy has emerged as one of the most popular medications for type 2 diabetes. We have previously reported that the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin attenuates neointima formation after vascular injury in non-diabetic mice. In the present study, we examined whether combined treatment with linagliptin and the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin attenuates neointima formation in diabetic mice after vascular injury. Diabetic db/db mice were treated with 3 mg/kg/day linagliptin and/or 30 mg/kg/day empagliflozin from 5 to 10 weeks of age. Body weight was significantly decreased by empagliflozin and the combined treatment. Blood glucose levels and glucose tolerance test results were significantly improved by empagliflozin and the combined treatment, but not by linagliptin. An insulin tolerance test suggested that linagliptin and empagliflozin did not improve insulin sensitivity. In a model of guidewire-induced femoral artery injury in diabetic mice, neointima formation was significantly decreased in mice subjected to combined treatment. In an in vitro assay using rat aortic smooth muscle cells (RASMC), 100, 500, or 1000 nM empagliflozin significantly decreased the RASMC number in a dose-dependent manner. A further significant reduction in RASMC proliferation was observed after combined treatment with 10 nM linagliptin and 100 nM empagliflozin. These data suggest that combined treatment with the DPP-4 inhibitor linagliptin and SGLT2 inhibitor empagliflozin attenuates neointima formation after vascular injury in diabetic mice in vivo and smooth muscle cell proliferation in vitro.     

Study of insulin response to oral glucose load after acute and chronic glycemic control in type 2 diabetic subjects

To investigate whether correction of fasting hyperglycemia per se improves the insulin secretion in type 2 diabetic subjects, plasma insulin response to 75 g oral glucose load has been studied after acute and chronic normalization of fasting plasma glucose levels in 7 overt type 2 diabetic subjects. For the acute normalization of elevated fasting plasma glucose levels, an artificial endocrine pancreas was employed. Although fasting plasma glucose concentrations were normalized before the oral glucose challenge, insulin response to oral glucose was not improved compared to those without normalization of fasting plasma glucose levels. After 1-3 month control of hyperglycemia, the insulin response to glucose in the subjects was significantly improved compared to those without treatments. Results indicate that chronic metabolic control is essential for the improvement of insulin response to glucose in type 2 diabetic subjects, and also suggest that the impaired insulin secretion in type 2 diabetes is not due to hyperglycemia per se, but due to the metabolic derangements which lead to chronic hyperglycemia.     

Zinc transporter gene expression and glycemic control in post-menopausal women with Type 2 diabetes mellitus

Type 2 diabetes mellitus (DM) is associated often with underlying zinc deficiency and nutritional supplements such as zinc may be of therapeutic benefit in the disease. In a randomized, double-blind, placebo-controlled, 12-week trial in postmenopausal women (n = 48) with Type 2 DM we investigated the effects of supplementation with zinc (40 mg/d) and flaxseed oil (FSO; 2 g/d) on the gene expression of zinc transporters (ZnT1, ZnT5, ZnT6, ZnT7, ZnT8, Zip1, Zip3, Zip7, and Zip10) and metallothionein (MT-1A, and MT-2A), and markers of glycemic control (glucose, insulin, glycosylated hemoglobin [HbA1c]). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. No significant effects of zinc or FSO supplementation were observed on glycemic marker concentrations, HOMA-IR or fold change over 12 weeks in zinc transporter and metallothionein gene expression. In multivariate analysis, the change over 12 weeks in serum glucose concentrations (P = 0.001) and HOMA-IR (P = 0.001) predicted the fold change in Zip10. In secondary analysis, marginal statistical significance was observed with the change in both serum glucose concentrations (P = 0.003) and HOMA-IR (P = 0.007) being predictive of the fold change in ZnT6. ZnT8 mRNA expression was variable; HbA1c levels were higher (P = 0.006) in participants who exhibited ZnT8 expression compared to those who did not. The significant predictive relationships between Zip10, ZnT6, serum glucose and HOMA-IR are preliminary, as is the relationship between HbA1c and ZnT8; nevertheless the observations support an association between Type 2 DM and zinc homeostasis that requires further exploration.     

Treatment with an Interleukin 1 beta antibody improves glycemic control in diet-induced obesity

The proinflammatory cytokine Interleukin 1 beta (IL-1beta) is elevated in obese individuals and rodents and it is implicated in impaired insulin secretion, decreased cell proliferation and apoptosis of pancreatic beta cells. In this study we describe the therapeutic effects by an IL-1beta antibody to improve glucose control in hyperglycemic mice with diet-induced obesity. After 13 weeks of treatment the IL-1beta antibody treated group showed reduced glycated hemoglobin (( *)P=0.049), reduced serum levels of proinsulin (( *)P=0.015), reduced levels of insulin and smaller islet size (( *)P=1.65E-13) relative to the control antibody treated group. Neutralization of IL-1beta also significantly reduced serum amyloid A (SAA) which is an indicator of inflammation-induced acute phase response (( *)P=0.024). While there was no improvement of obesity, a significant improvement of glycemic control and of beta cell function is achieved by this pharmacological treatment which may slow/prevent disease progression in Type 2 Diabetes.