Identifying the links between obesity,insulin resistance and beta-cell function: potential role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes

A combination of insulin resistance and pancreatic beta-cell dysfunction underlies most cases of type 2 diabetes. While the interplay of these two impairments is believed to be important in the development and progression of type 2 diabetes, the mechanisms involved are unclear. A number of factors have been suggested as possibly linking insulin resistance and beta-cell dysfunction in the pathogenesis of type 2 diabetes mellitus. Pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) have deleterious effects on both glucose homeostasis and beta-cell function, and can disrupt insulin signalling pathways in both pancreatic beta cells and liver and adipose tissue. The anti-inflammatory activity of the thiazolidinedione anti-diabetic agents is potentially beneficial, given the possible role of pro-inflammatory cytokines in linking insulin resistance with beta-cell dysfunction.     

Pioglitazone shift circadian rhythm of blood pressure from non-dipper to dipper type in type 2 diabetes mellitus

BACKGROUND: Insulin resistance significantly correlated with a non-dipper type of essential hypertension. Thiazolidinediones (TZD), oral hypoglycaemic agents that act as insulin sensitizers, have been demonstrated in multiple in vivo and in vitro studies to possess antihypertensive properties. This study examined the efficacy of TZD therapy with pioglitazone at transforming the circadian rhythms of blood pressure from a non-dipper to a dipper type. MATERIALS: We examined 31 patients with type 2 diabetes mellitus during both a baseline period and a period of treatment with pioglitazone. Patients received 15 mg day(-1) pioglitazone for four weeks and 30 mg day(-1) for 12 weeks. Twenty-four hour ambulatory blood pressure monitoring (ABPM) and laboratory data (blood tests for cardiovascular risk factors) were obtained at the beginning and end of the study. RESULTS: In non-dippers (n = 16), but not dippers (n = 15), we observed a significant interaction between pioglitazone therapy and nocturnal falls in systolic and diastolic blood pressure. This examination indicated that the magnitude of the nocturnal blood pressure fall was affected by pioglitazone therapy. In non-dippers, but not dippers, a significant correlation was observed between the percent decrease in nocturnal BP and the homeostasis model assessment (HOMA) index (r = 0.774, P = 0.0007). CONCLUSIONS: The present study demonstrated that pioglitazone can restore the nocturnal BP declines in parallel to reductions in the HOMA index, suggesting that insulin resistance may play an important role in the genesis of circadian BP rhythms. TZD-based treatment may thus have the additional therapeutic advantage of reducing the risk of cardiovascular complications by transforming the circadian rhythm of BP.     

Beta-cell response to metformin-glibenclamide combination tablets (Glucovance) in patients with type 2 diabetes

This exploratory double-blind, randomised, 20-week study evaluated the mechanism of action of metformin-glibenclamide combination tablets (Glucovance) vs. metformin and glibenclamide in 50 type 2 diabetes patients inadequately controlled by diet and exercise. A glycaemic target of HbA1C 7.0% was used. Final HbA(1C), fasting glucose and post-oral glucose tolerance test (OGTT) glucose were similar between groups, although average doses of metformin and glibenclamide from combination tablets (708 and 3.5 mg) were lower than monotherapy doses (1500 and 6.6 mg). Second-phase insulin during a hyperglycaemic clamp increased by 93% with combination tablets, 36% with metformin and 46% with glibenclamide. The insulin response post-OGTT was more rapid with the combination tablets vs. glibenclamide. First-phase insulin responses improved modestly in all groups, possibly due to reduced glucotoxicity. Changes in insulin sensitivity were minor. Larger beta-cell responses between combination tablets and glibenclamide may reflect more rapid glibenclamide absorption.     

早期强化与常规治疗对初诊2型糖尿病患者P细胞功能与胰岛素抵抗的影响比较

目的探讨强化治疗与常规治疗对初诊T2DM患者胰岛口细胞功能与胰岛素抵抗（IR）的影响比较。方法将2012年4月一2013年4月在本院内分泌科诊治的56例初诊2型糖尿病患者随机分为强化组和常规治疗组。强化组应用胰岛素泵,常规治疗组应用降糖药物治疗,连续治疗4个疗程。比较2组患者治疗前后HjG、HbAlc、TC、TG、HDL—C、LDL—C、HOMA-β、HOMA-IR的水平。结果治疗后2组患者血清TC、TG、HDL-C、LDL-C较同组治疗前有明显改善（P〈0．05或P〈0．01）,FBG、HbAIc、HOMA-β、HOMA-IR较治疗前有显著差异（P〈0．05或P〈0．01）。结论早期胰岛素泵强化治疗可以有效控制血糖,降低血脂,改善胰岛素抵抗,恢复胰岛口细胞功能,缓解2型糖尿病的临床症状,减缓2型糖尿病的病程。     

2型糖尿病新发患者血清25羟维生素D_3的水平及临床意义

目的探讨2型糖尿病(T2DM)新发患者血清25羟维生素D_3[25-(OH)D_3]的水平,以及25-(OH)D_3与B细胞功能、胰岛素抵抗的关系。方法选取2013年1月至2016年6月于南京市中医院住院的T2DM新发患者48例为观察组,同时选取同期年龄匹配的健康体检者40例为对照组,留取血清及血浆标本测定空腹血糖(FBG)、空腹胰岛素(FIns)、血脂、糖化血红蛋白(HbA1c)以及血清25-(OH)D_3水平。比较两组间胰岛素抵抗指数(HOMA-IR)、胰岛B细胞功能指数(HOMA-β)及25-(OH)D_3等指标的差异,并分析25-(OH)D_3与HOMA-IR、HOMA-β的相关性。结果观察组FBG、血脂、HbA1c、HOMA-IR均高于对照组,且差异具有统计学意义(P0.05),而血清25-(OH)D_3水平、HOMA-β均低于对照组,且差异具有统计学意义(P0.05)。新发T2DM组患者血清25-(OH)D_3水平与FBG、HbA1c、HOMA-IR呈负相关(r值分别为-0.30,-0.34,-0.23,P0.05),与HOMA-β呈正相关(r=0.27,P0.05)。结论新发T2DM患者较对照组存在25-(OH)D_3水平低下,且血清25-(OH)D_3水平的降低与胰岛素抵抗和胰岛B细胞分泌功能下降有关。补充维生素D可能使患者获益。     

Evaluating the cost-effectiveness of therapy conversion to insulin detemir in patients with type 2 diabetes in Germany: a modelling study of long-term clinical and cost outcomes

OBJECTIVES: To evaluate the long-term cost-effectiveness of transferring type 2 diabetes patients to an insulin detemir regimen after failure to achieve adequate control with oral antidiabetic agents (OADs) alone, or in combination with neutral protamine hagedorn (NPH) insulin, or with insulin glargine in Germany. METHODS: A computer simulation model of diabetes was used to make long-term projections of future clinical outcomes and direct medical costs based on findings from a German subanalysis of the PREDICTIVE trial. The study analysed the impact of converting patients failing their current treatments to an insulin detemir regimen. Therapy conversion to insulin detemir +/- OADs was associated with a significant reduction in glycosylated haemoglobin (HbA(1)c) compared with OADs alone, NPH insulin +/- OADs, and insulin glargine +/- OADs. Across all three groups, hypoglycaemia rates decreased by 80% and patients lost an average of 0.9 kg of body weight during treatment with insulin detemir +/- OADs. RESULTS: Therapy conversion to insulin detemir +/- OADs was projected to improve life expectancy by 0.28 years compared with OADs alone, and by 0.13 years compared with the NPH and glargine regimens. Transfer to insulin detemir was associated with improvements in quality-adjusted life expectancy of 0.21 quality-adjusted life years (QALYs) over OADs alone, 0.28 QALYs over NPH +/- OADs, and 0.29 QALYs over glargine +/- OADs. Insulin detemir was associated with savings over patient lifetimes due to reduced diabetes-related complications in all three comparisons. CONCLUSIONS: Therapy conversion to insulin detemir +/- OADs in type 2 diabetes patients failing OADs alone, NPH or insulin glargine regimens was associated with improvements in life expectancy, quality-adjusted life expectancy and cost savings in all three scenarios evaluated.     

血清铁蛋白与2型糖尿病关系的研究

目的探讨血清铁蛋白与2型糖尿病的关系。方法对80例2型糖尿病患者以及69例健康体检者分别测定身高、体重、腰围、臀围、血压;空腹血糖、口服75 g葡萄糖粉测量2小时血糖、空腹胰岛素、血清铁蛋白、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白及C反应蛋白浓度。计算体重指数、腰臀围比及胰岛素抵抗指数。结果与对照组相比,初诊的2型糖尿病患者具有较高的BMI、WHR、FINS、TG、C-RP以及SBP水平(P<0.05);HOMA-IR明显升高(P<0.05);较低的HDL-C水平(P<0.05);而TC、LDL-C水平及DBP无明显差异(P>0.05);糖尿病组不论男性与女性SF浓度明显高于对照组(P<0.05)。通过直线相关分析可知,经对数转换后的2型糖尿病患者SF与TC、TG、LDL-C、C-RP呈正相关(P<0.05);与FBG、PBG、HOMR-IR及DBP显著正相关(P<0.01);与HDL-C呈负相关(P<0.05);与SBP、BMI、WHRF、INS非线性关系。经多因素逐步回归分析发现血清铁蛋白是参与HOMR-IR的独立变量。结论本研究证实2型糖尿病患者体内铁超负荷;而铁超负荷可能是导致胰岛素抵抗,促进糖尿病发生的许多重要的危险因素之一;并且血清铁蛋白可以预测糖尿病代谢控制程度。     

血清维生素D检测对2型糖尿病患者的临床意义

目的探讨2型糖尿病患者血清维生素D（VD）水平的变化,以及VD水平与胰岛素分泌及胰岛素抵抗的关系。方法随机选取2011年7～12月在本院住院确诊为2型糖尿病的患者56例。所有患者均符合世界卫生组织糖尿病的临床诊断标准。设正常糖耐量对照组53例,测定血清中VD水平,比较两组VD水平的差异。在糖尿病患者中分别用稳态模式评估法公式HOMA—IR和HOMA—B估测胰岛素敏感性及胰岛β细胞功能,分析VD浓度与HOMA—IR及HOMA—β的相关性。结果糖尿病患者组较正常糖耐量组血清VD水平显著下降（P〈0．05）;VD水平与HOMA—B呈正相关（r=0．48）,VD水平与HOMA—IR无关（r=-0．08）。结论2型糖尿病患者存在VD缺乏,VD水平影响胰岛B细胞分泌功能,补充VD可能成为糖尿病治疗手段之一。     

Variation of inflammatory parameters after sibutramine treatment compared to placebo in type 2 diabetic patients

What is known and Objective: The efficacy of sibutramine has been demonstrated in randomized trials in obese/overweight patients including those with type 2 diabetes mellitus (T2DM). Our objective was to evaluate the effects of 1‐year treatment with sibutramine compared to placebo on body weight, glycaemic control, lipid profile, and inflammatory parameters in type 2 diabetic patients. Methods: Two hundred and forty‐six patients with uncontrolled T2DM [glycated haemoglobin (HbA_1c) >8·0%] in therapy with different oral hypoglycaemic agents or insulin were randomized to take 10 mg of sibutramine or placebo for 12 months. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA_1c, fasting plasma glucose (FPG), post‐prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA‐IR), total cholesterol (TC), low density lipoprotein‐cholesterol (LDL‐C), high density lipoprotein‐cholesterol (HDL‐C), triglycerides (Tg), leptin, tumour necrosis factor‐α (TNF‐α), adiponectin (ADN), vaspin, high sensitivity C‐reactive protein (Hs‐CRP). Results and Discussion: We observed a decrease of body weight after 9 and 12 months in the group treated with sibutramine, but not in the control group. Regarding glycaemic and lipid profile, although there are differences seen over time within each of the groups, we did not obtain any significant differences between the two groups. Both placebo and sibutramine gave a similar improvement of HOMA‐IR, leptin, TNF‐α, ADN, and Hs‐CRP. No vaspin variations were observed in either group. What is new and Conclusion: Sibutramine resulted in a decrease in body weight at 9 months and at 12 months that was not observed with placebo. Although there were differences seen over time within each of the groups, there were no significant differences between groups for any other parameter that we measured.     

A Rice Bran Oil Diet Improves Lipid Abnormalities and Suppress Hyperinsulinemic Responses in Rats with Streptozotocin/Nicotinamide-Induced Type 2 Diabetes

The aim of this study was to determine the effects of rice bran oil (RBO) on lipid metabolism and insulin resistance in rats with streptozotocin/nicotinamide-induced type 2 diabetes mellitus (T2DM). Rats were divided into two groups: the control group (15% soybean oil, contains 0 g γ-oryzanol and 0 g γ-tocotrienol/150 g oil for 5 weeks) and the RBO group (15% RBO, contains 5.25 g γ-oryzanol and 0.9 g γ-tocotrienol/150 g oil for 5 weeks). Compared with the control group, the RBO group had a lower plasma nonesterified fatty acid concentration, ratio of total to high-density-lipoprotein cholesterol, hepatic cholesterol concentration, and area under the curve for insulin. The RBO group had a higher high-density-lipoprotein cholesterol concentration and greater excretion of fecal neutral sterols and bile acid than did the control group. RBO may improve lipid abnormalities, reduce the atherogenic index, and suppress the hyperinsulinemic response in rats with streptozotocin/nicotinamide-induced T2DM. In addition, RBO can lead to increased fecal neutral sterol and bile acid excretion.     

Intensification of insulin therapy in patients with type 2 diabetes mellitus: An algorithm for basal-bolus therapy

Abstract

The incidence of diabetes mellitus is projected to continue to increase worldwide over the next 20 years leading to increased costs in the management of the disease and its associated co-morbidities. Insulin replacement is one of many treatment options that can help to bring about near normoglycemia in the patient with type 2 diabetes mellitus (T2DM). Glycemic control as close to normoglycemia as possible can help to reduce the risk of microvascular and macrovascular complications, yet less than one-half of patients with T2DM achieve glycemic targets as recommended by practice guidelines. The purpose of this review is to provide guidance to primary care physicians for the initiation and intensification of basal-bolus insulin therapy in patients with T2DM. Two treatment algorithms that can be both patient- and physician-driven are proposed: a stepwise approach and a multiple daily injections approach. Evidence shaping the two approaches will be discussed alongside management issues that surround the patient treated with insulin: hypoglycemia, weight gain, patient education, and quality of life.     

Subcutaneous lispro and intravenous regular insulin treatments are equally effective and safe for the treatment of mild and moderate diabetic ketoacidosis in adult patients

In this prospective, randomised, open trial, we wanted to evaluate the efficacy and safety of hourly subcutaneous (SC) insulin lispro administration in the treatment of diabetic ketoacidosis (DKA) in comparison with intravenous (IV) regular insulin treatment. Twenty patients were enrolled in the study. The patients were randomly assigned into two groups. Following a bolus injection of 0.15 U/kg IV regular insulin, group L received half of this dose as hourly SC insulin lispro while group R was treated conventionally with IV regular insulin infusion. At the end of treatment period, time that needed for normalisation of serum glucose, beta-hydroxybutyrate, blood pH and urine ketone levels were not different in groups L and R. There was no mortality or serious side effects in both groups. In this study, we revealed that treatment of mild and moderate DKA with SC insulin lispro is equally effective and safe in comparison with IV regular insulin.     

两种胰岛素类似物治疗2型糖尿病的比较

目的探讨预混胰岛素类似物门冬胰岛素30注射液（诺和锐30）和长效胰岛素类似物甘精胰岛素注射液（来得时）治疗2型糖尿病的疗效和安全性。方法 83例初诊2型糖尿病随机分成2组,分别给予诺和锐30每天2次及来得时每天1次治疗12周,观察治疗前后空腹血糖（FPG）、餐后2小时血糖（PPG）、糖化血红蛋白（HbA1c）的变化,比较两组血糖达标率、低血糖的发生率。结果诺和锐30组HbA1c较来得时治疗组明显下降,HbA1c（7.42±1.38）%vs（8.31±1.82）%（P〈0.05）。诺和锐30组PPG显著低于来得时组,（7.82±4.18）mmol/L vs（8.21±3.90）mmol/L（P〈0.05）。诺和锐30组PPG达标率更高,83.0%vs 56.1%（P〈0.05）,达标时间更短,（7.85±1.48）天vs（8.25±2.46）天,但低血糖事件较来得时组略高,26.2%vs 12.2%（P〈0.05）。诺和锐30组胰岛素用量高于来得时组,（0.61±0.24）U/kg vs（0.50±0.27）U/kg（P〈0.05）,体质量增加也较明显,（5.6±4.6）kg vs（3.0±4.3）kg（P〈0.05）。结论诺和锐30每天2次治疗比来得时每天1次治疗能更有效地降低血糖,血糖达标时间更短,但低血糖发生率略高。