Impact of waist/height ratio on insulin resistance and function of pancreatic β-cells in newly diagnosed Type 2 diabetes mellitus

Objective To study the impact of central obesity on insulin resistance and the function of pancreaticβcells in newly diagnosed Type 2 diabetes. Methods Eighty-six type 2 diabetes mellitus (T2DM) patients were divided into 2 groups according to their waist to hip ratio. Metabolic parameters and Insulin resistance and the function of pancreatic β-cells were compared. Insulin resistance were calculated by HOMA-IR and the function of pancreatic β-cells were detected by HOMA-βand ISF-Arg. Results HOMA-IR index, HOMA-IS and ISF-Arg in WHR ≥0.85 (male) or 0.80 (female) group were significantly higher than that of WHR ＜ 0. 85 (male) or 0. 80 (female) group ( P ＜ 0. 01 ), whereas WHR ＜ 0. 85 (male) or 0. 8 ( female ) group had significantly higher fasting sugar levels and HbA1c and favorable lipid profile (P ＜ 0.05 ). Conclusion WHR is an useful parameter in roughly judging the function of β-cell and insulin resistance.     

Impact of waist/height ratio on insulin resistance and function of pancreatic β-cells in newly diagnosed Type 2 diabetes mellitus

Objective To study the impact of central obesity on insulin resistance and the function of pancreaticβcells in newly diagnosed Type 2 diabetes. Methods Eighty-six type 2 diabetes mellitus (T2DM) patients were divided into 2 groups according to their waist to hip ratio. Metabolic parameters and Insulin resistance and the function of pancreatic β-cells were compared. Insulin resistance were calculated by HOMA-IR and the function of pancreatic β-cells were detected by HOMA-βand ISF-Arg. Results HOMA-IR index, HOMA-IS and ISF-Arg in WHR ≥0.85 (male) or 0.80 (female) group were significantly higher than that of WHR ＜ 0. 85 (male) or 0. 80 (female) group ( P ＜ 0. 01 ), whereas WHR ＜ 0. 85 (male) or 0. 8 ( female ) group had significantly higher fasting sugar levels and HbA1c and favorable lipid profile (P ＜ 0.05 ). Conclusion WHR is an useful parameter in roughly judging the function of β-cell and insulin resistance.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Effects of stilbenes on glucose and lipid metabolism in insulin resistant HepG2 cells北大核心CSCD

Aim To explore the effect of four stilbenes including rhaponticin, desoxyrhaponticin, rhapontigenin and resveratrol on glucose and lipid metabolism in insulin-resistant HepG2 cells induced by high glucose and high fat. Methods The model of insulin resistance was established by incubating HepG2 cells with a complex of glucose and oleic acid. MTT assay was used to detect cell viability. The intracellular triglyceride (TG) and glucose levels were measured by the kit method. The lipid production was observed by oil red O staining, and the cell morphology and uptake of 2-NBDG were observed by confocal microscope. The PPAR signaling pathway and PI3K/Akt insulin signaling pathway related proteins were determined by Western blot to evaluate the effect of stilbenes on glycolipid metabolism in IR-HepG2 cells. Results The complex containing 50 mmol • L-1 glucose and 0.5 mmol • L-1 oleic acid induced a successful insulin resistance model in HepG2 cells for 48 hours. Compared with the model group, all the four compounds could reduce the content of TG and lipid accumulation, and increase the ability of glucose uptake. These compounds could significantly inhibit the expression level of peroxisome proliferatorsactivated receptor (PPAR-) lipid metabolism-related proteins, and up-regulate the expression of phosphoinositide 3 -kinase (PI3 K) glycometabolism-related proteins, among which rhaponticin and resveratrol had the most significant effect. Conclusions The four stilbenes may alleviate insulin resistance in HepG2 cells by regulation of glucose and lipid metabolism disorder, especially rhaponticin and resveratrol. The mechanism may be related to the regulation of PPAR signaling pathway and the activation of PI3 K/AKT/mTORl pathway to reduce lipid production and promote glucose uptake. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Dysfunction in the β2-adrenergic signal pathway in patients with insulin dependent diabetes mellitus (IDDM) and unawareness of hypoglycaemia

The majority of the impaired symptoms in hypoglycaemia unawareness, such as palpitations, tachycardia and tremor, are caused by increased release of adrenaline (ADR) and noradrenaline (NA), and induced by stimulation of -adrenergic receptors. Binding of ADR or NA to the -adrenergic receptor generates a signal, transmitted via a guanine nucleotide binding protein complex (G-protein), which in turn activates adenylate cyclase with increased production of cAMP. The aim of this study was to show whether IDDM-patients with hypoglycaemia unawareness had deficient coupling between ₂-adrenergic receptors and G-proteinscompared to IDDM-patients with hypoglycaemia awareness and healthy controls. The IDDM-patients were subgrouped as hypoglycaemia aware or unaware based on questionnaire answers, clinical information and the results of isoprenaline sensitivity tests. Mononuclear leukocytes (MNL) were isolated from venous blood. By saturation binding experiments, using [¹²⁵I]-(-)-iodopindolol ((-)-IPIN), total receptor number (B_max) and affinity (K_d) were determined. By displacement experiments the relative number of low-and high-affinity receptors for the -adrenergic agonist (-)-isoprenaline ((-)-ISO) were determined. We found no difference in B_max- or K_d-values for (-)-IPIN between the subgroups. However, there was a reduced capability to form high-affinity binding complexes with (-)-ISO in MNL from IDDM-patients with hypoglycaemia unawareness. It was concluded that hypoglycaemia unawareness in IDDM was associated with dysfunction of the proximal ₂-adrenergic signal pathway.     

Beta-blockers in the management of hypertension in patients with type 2 diabetes mellitus: is there a role?

It has been conclusively established that treatment of hypertension in patients with type 2 (non-insulin-dependent) diabetes mellitus will significantly reduce the incidence of stroke, heart failure and progression of diabetic complications. Beta-blockers are effective antihypertensive agents which, in long term studies, have proven beneficial in reducing important clinical end-points. However nonselective beta-blockers may have a negative effect on lipid profiles and contribute to hypoglycaemic unawareness, thus preventing their use in some patients with diabetes mellitus. The development of newer and more selective beta-blockers has overcome many of these problems. In addition, some of the newer agents have novel properties such as release of nitric oxide, which theoretically would make them more attractive in patients with diabetes mellitus. Overall, the adverse metabolic effects of beta-blockers do not appear to be important in clinical practice and these agents should no longer be contraindicated in patients with type 2 diabetes mellitus. Their proven cardiovascular benefits would seem to easily tip the balance in favour of their use.     

The impact of type Ⅱ diabetes mellitns and isolated impaired glucose tolerance on severity and prognosis of patients with acute cerebral infarction

目的 探讨2型糖尿病(T2DM)及单纯性糖耐量受损(I-IGT)对急性脑梗死患者病情及预后的影响.方法 根据血糖情况,将195例急性脑梗死患者分为血糖正常组(54例)、T2DM组(63例)和I-IGT组(78例).采用美国国立卫生院卒中评分量表(NIHSS)评估患者人院时及入院1周时的病情.采用改良Rankin评分量表(mRS)于发病后1个月、3个月评估患者的预后.结果 三组患者人院时NIHSS评分相仿(P＞0.05);入院1周时,T2DM组和I-IGT组NIHSS评分均显著高于正常组(P＜0.05).T2DM组发病后1个月、3个月的预后不良率分别为57.1％、44.4％,I-IGT组分别为48.7％、41.0％,均明显高于与正常组的31.5％、20.4％(P＜0.05).T2DM组与I-IGT组并发症发生率分别为77.8％和70.5％,亦明显高于与正常组的27.8％(P＜0.05).结论 T2DM及I-IGT使急性脑梗死患者病情加重,预后不良.     

Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large,international population

Abstract

Objective:

To examine the scope and underpinnings of psychological insulin resistance (PIR) across eight Western nations, with special attention to the potential influence of beliefs about insulin and broader patient beliefs regarding medications and diabetes.     

Once-daily insulin detemir in a cohort of insulin-naïve patients with type 2 diabetes: a sub-analysis from the PREDICTIVE study

ABSTRACT

Objective: PREDICTIVE^* is a large, observational study of the empirical use of insulin detemir in patients with type 1 or type 2 diabetes (T1DM/T2DM). This post hoc analysis evaluates insulin-naïve patients with T2DM uncontrolled on oral antidiabetic drugs (OADs) who were initiated and remained on once-daily insulin detemir for 12 weeks.

Research design and methods: This observational, multinational, multi-center, open-label prospective study evaluated the efficacy and safety of insulin detemir in 1653 insulin-naïve patients with T2DM (mean age 60.8?±?10.9 years, BMI 29.8?±?4.8?kg/m², and HbA_1C 8.82?±?1.50%). Statistical comparisons were made between baseline and 12-week follow up data. Our study was subject to the usual limitations of observational studies.

Main outcome measures: Endpoints were: incidence of serious adverse drug reactions, including number of hypoglycemic events (total, major, and nocturnal), glycemic parameters, and weight change.

Results: Following insulin initiation, no significant change occurred in the number of nocturnal hypoglycemic events or total hypoglycemic events (p?=?0.4513), and no serious adverse drug reactions were observed during the 12 weeks of treatment. HbA_1C decreased by a mean 1.25% (SD?±?1.25%; p?<?0.0001), with 30% of patients (n?=?383) achieving HbA_1C <7% at 12 weeks. Mean changes in fasting blood glucose and fasting blood glucose variability were –3.62?mmol/L (SD?±?2.93; p?<?0.0001) and ?0.48?mmol/L (SD?±?1.03; p?<?0.0001), respectively. Body weight decreased by a mean 0.5?kg (SD?±?3.3; p?<?0.0001), with weight loss or no weight change occurring in a substantial percentage of patients in each BMI category (<25, 25–30, 30–35, and >35?kg/m²). Patients with higher baseline BMI lost the most weight, with the greatest weight loss (–1.20?kg) reported in those with BMI >35?kg/m².

Conclusions: Empirical use of insulin detemir as an insulin initiation strategy can improve glycemic control with good tolerability, including a low risk of hypoglycemia and a weight benefit, in a majority of insulin-naïve patients uncontrolled on OADs.     

Adverse drug reactions associated with the use of liraglutide in patients with type 2 diabetes – focus on pancreatitis and pancreas cancer

Introduction: The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, is a widely used drug for the treatment of type 2 diabetes. Liraglutide is one of several incretin-based agents that have been suggested to be associated with pancreatitis and pancreas cancer. The suspicion accelerated after publication of an autopsy study claiming increased incidences of several pathological changes in pancreata from patients with diabetes treated with incretin-based drugs.

Areas covered: The aim of the present review is to give an overview of the pharmacology of liraglutide and provide a review of adverse reactions associated with liraglutide with a focus on the risk of pancreatitis and pancreas cancer.

Expert opinion: When comprehensively reviewing the available literature, no clear and significant associations between liraglutide and pancreatitis and/or pancreas cancer seem evident. However, a recently published analysis suggests a trend toward a slightly elevated risk of pancreatitis with GLP-1 receptor agonists (including liraglutide), which may become statistical significant as more data become available. Well-established side effects are of gastrointestinal origin, typical mild-to-moderate and of transient character. The risk of hypoglycemia associated with liraglutide treatment is low.     

Angiotensin Ⅱ receptor blocker provides pancreatic β-cell protection independent of blood pressure lowering in diabetic db/db mice1

AIM: Several epidemiological studies have suggested that treatment with angiotensin II type 1 receptor blocker provided a risk reduction of developing type 2 diabetes. The aim of this study was to investigate whether and how chronic candesartan treatment can attenuate the deleterious influence of the hyperactive local intra-islet renin-angiotensin system in the diabetes state. METHODS: Eight-week-old db/db mice were randomized to candesartan 1 mg/kg, candesartan 10 mg/kg, manidipine 10 mg/kg, or placebo via gavage for 6 weeks. Their age-matched nondiabetic littermates db/m mice were treated with placebo and acted as nondiabetic controls. After 6 weeks' treatment, an intraperitoneal glucose tolerance test, immunohistochemical staining of oxidative stress markers, insulin, CD31, azan staining and an electron microscopy observation were performed. RESULTS: Chronic candesartan treatment provided an improvement of glucose tolerance, and greatly rescued islet beta-cell mass. Candesartan treatment also notably decreased staining intensity of oxidative stress markers, as well as attenuating intra-islet fibrosis and improving blood supply in the islet. In the electron microscopy observation, candesartan-treated animals exhibited improved granulation and less remarkable endoplasmic reticulum and Golgi bodies; furthermore, candesartan treatment greatly relieved the swelling of mitochondria to nearly normal. Both the benefits of reducing oxidative stress and ultrastructure protection were in a dose-dependent and blood pressure-independent manner. CONCLUSION: After diabetes was initiated, candesartan treatment could not reverse the state of diabetes, but it effectively improved glucose tolerance and protected beta-cell function by attenuating oxidative stress, islet fibrosis, sparsity of blood supply and ultrastructure disruption in a dose-dependent and blood pressure-independent manner.     

Long-term clinical and cost outcomes of treatment with biphasic insulin aspart 30/70 versus insulin glargine in insulin naïve type 2 diabetes patients: cost-effectiveness analysis in the UK setting

OBJECTIVES: To evaluate the long-term clinical and cost outcomes associated with biphasic insulin aspart 30/70 (BIAsp 30/70, premixed 30% soluble and 70% protaminated insulin aspart in one injection) compared to insulin glargine treatment in insulin-na?ve type 2 diabetes patients failing oral antidiabetic agents in the UK, based on findings recently reported from the INITIATE clinical trial. METHODS: The CORE Diabetes Model, a published, peer-reviewed and validated model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy, cumulative incidence of complications and direct medical costs over patient lifetimes. The model simulates the range of diabetic complications and disease progression within a series of sub-models (cardiovascular disease, neuropathy, renal and eye disease) based on published data. Baseline cohort characteristics (54.5% male, mean age 52.45 years, mean diabetes duration 9 years, mean HbA(1c) 9.77%) and treatment effects were based on INITIATE. Costs were derived from published UK sources. The analysis was run over a 35-year time horizon (patient lifetime) from a third party payer perspective. Costs and clinical benefits were discounted at 3.5% per annum. Sensitivity analyses were performed. RESULTS: BIAsp 30/70 was associated with projected improvements in discounted life expectancy (0.19 +/- 0.20 years) and quality-adjusted life expectancy (0.19 +/- 0.14 quality-adjusted life years [QALYs]), as well as a reduced incidence of retinopathy and nephropathy complications, versus glargine. Total lifetime direct costs were 1319 pounds higher with BIAsp 30/70 than with glargine leading to an incremental cost-effectiveness ratio of 6951 pounds per QALY gained. CONCLUSIONS: This study is the first to address the long-term health economic implications of treating type 2 diabetes patients failing oral anti-diabetics with a biphasic insulin mix versus long-acting insulin. Our projections indicate that improved HbA1c levels with BIAsp 30/70 treatment are associated with improvements in life expectancy and quality-adjusted life expectancy, and that BIAsp 30/70 represents excellent value for money compared to insulin glargine in the UK.