Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes

The aim of this study was to evaluate the effects of pioglitazone on clinical and metabolic parameters, body fat distribution, and serum adiponectin, a recently discovered antiatherosclerotic hormone, in Japanese patients with type 2 diabetes. Ten male patients aged 40 to 66 (57.7 +/- 7.4) years, who were being treated with dietary therapy alone (n = 7) or with a stable dose of sulfonylurea (n = 3), were studied at baseline and after 3 months of pioglitazone treatment (30 mg/d). Body mass index (BMI), blood pressure, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), serum insulin, adiponectin, and lipid profile were measured. Also, visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) at the umbilical level were determined by computed tomographic (CT) scanning. Mean blood pressure (109 +/- 14 to 101 +/- 10 mm Hg), FPG (8.6 +/- 1.4 to 7.0 +/- 1.0 mmol/L), serum insulin (54 +/- 11 to 30 +/- 8 pmol/L, P <.01 for all), and HbA1c (6.7 +/- 0.8 to 6.1% +/- 0.6%, P =.013) decreased significantly during 3 months of pioglitazone treatment. BMI (26.4 +/- 3.2 to 27.0 +/- 3.5 kg/m2), low-density lipoprotein (LDL) cholesterol (124 +/- 24 to 138 +/- 24 mg/dL) and SAT (155 +/- 69 to 179 +/- 81cm2, P <.05 for all) increased, while triglycerides and high-density lipoprotein (HDL) cholesterol did not change significantly after 3 months of pioglitazone treatment. Serum adiponectin level increased in all patients (4.8 +/- 1.7 to 14.4 +/- 2.1 microg/mL, P =.005). VAT tended to increase (165 +/- 38 to 180 +/- 46 cm2) and VAT/SAT ratio tended to decrease (1.2 +/- 0.3 to 1.1 +/- 0.3), but these differences did not reach statistical significance. These results suggest that pioglitazone exerts good glycemic and blood pressure control despite increased BMI and SAT in Japanese male patients with type 2 diabetes. It is also suggested that pioglitazone may have an antiatherosclerotic effect by increasing serum adiponectin level.     

Effects of rosiglitazone on body fat distribution and insulin sensitivity in Korean type 2 diabetes mellitus patients

The objective of the study was to investigate the effects of rosiglitazone (RSG), a thiazolidinedione derivative, on body fat distribution and insulin sensitivity in Korean subjects with type 2 diabetes mellitus. This study was a phase IV, multicenter, single-blind, positive-controlled parallel group study. Eighty-nine patients with type 2 diabetes mellitus, aged 30 to 75 years, were enrolled in this study. Their fasting plasma glucose levels ranged from 126 to 270 mg/dL, and subjects had hemoglobin A1c levels of greater than 7.0%. We compared the effect of the treatment with glibenclamide plus RSG 4 mg/d (increased to 8 mg/d after 6 months) with glibenclamide plus placebo on body fat distributions, which were determined by computed tomography scanning and glycemic and insulinemic responses to oral glucose load. During the 12-month treatment period, the difference between the changes in the ratio of the intraabdominal adipose tissue (IAAT) to abdominal subcutaneous adipose tissue areas (SAT) between treatment groups was significant (from 1.13 +/- 0.53 to 1.00 +/- 0.40 in the RSG group and from 0.92 +/- 0.54 to 0.96 +/- 0.62 in the placebo group, P = .0351). The glycemic responses to oral glucose load (area under the curve, millimoles per liter per hour) were improved in the RSG group with 12 months of treatment (from 4.88 +/- 1.10 to 4.38 +/- 1.35 in 1 hour and from 13.78 +/- 2.83 to 12.16 +/- 2.52 in 2 hours), and the difference between the changes of the glycemic response showed statistical significance between groups (RSG group vs placebo group: -0.53 +/- 1.42 vs 0.38 +/- 1.31, difference in 1 hour; -0.76 +/- 2.98 vs 1.43 +/- 2.58, difference in 2 hours). However, there was no difference between insulin responses from baseline to follow-up and no differences in the change in insulin response between groups. In Korean subjects with type 2 diabetes mellitus, 12 months of treatment with RSG may increase SAT, but may have a neutral effect on IAAT, resulting in a decrease in the IAAT:SAT ratio. The RSG treatment improved the glucose control in type 2 diabetes mellitus. However, it is important to determine whether the glucose-lowering effect of RSG occurs mainly through direct enhancement of insulin sensitivity.     

Short-term treatment with troglitazone decreases bone turnover in patients with type 2 diabetes mellitus

Poorly controlled type 2 or non-insulin dependent diabetes mellitus (NIDDM) patients exhibit high bone turnover, which decelerate with treatment according to the degree of improvement in glycemic control. In adults, higher bone turnover results in rapid bone loss. Therefore, deceleration of bone turnover is beneficial for bone. Troglitazone (Tro), a new anti-diabetic drug, is a thiazolidinedione (TZD) which promotes adipocyte differentiation by activating peroxisome proliferator activated receptor gamma (PPARgamma). Because, in the bone marrow, adipocytes and osteoblasts originate in common mesenchymal stem cells that are also essential for osteoclastogenesis, TZDs may directly affect bone metabolism. Thus, we examined the effects of Tro on metabolic bone markers in type 2 DM patients. Tro (400 mg/day) was administered to 33 type 2 DM patients for four weeks. The day before and four weeks after starting Tro, serum and urine samples were collected after overnight fasting. Metabolic bone markers and glycemic indices were assessed. As bone resorption markers, urinary free and total deoxypyridinoline as well as urinary collagen type I C-terminal telopeptide were measured; as bone formation markers, serum bone type and total alkaline phosphatase (BALP and ALP) levels along with osteocalcin (OC) were used. No significant changes in fasting plasma glucose or HbA1c levels were observed in our short-term treatment with Tro. All the bone resorption markers, BALP and ALP were significantly decreased. OC was not significantly changed. The discrepant changes of OC from all the other metabolic bone markers suggest limitation of the use of OC as a reliable bone formation marker in diabetics. Our results that Tro decreased metabolic bone markers before significantly improving glucose metabolism suggest that it has direct effects on bone and decreased bone turnover. TZDs may spare bone mass in NIDDM subjects through its dual effects on glucose and bone metabolism.     

男性2型糖尿病患者体脂分布与心血管危险因素的关系

目的探讨男性2型糖尿病患者体脂分布特点及其与心血管危险因素的关系。方法横断面研究,用CT测量91例男性T2DM患者腹壁皮下脂肪面积（SA）及腹腔脏器脂肪面积（VA）,计算VA／SA（VSR）以及腹部总体脂量（TAF）,同时检测代谢参数,计算BMI;对体脂参数与代谢危险因素行peanson相关分析、偏相关分析及多元逐步回归分析。结果（1）相关分析结果显示,体脂分布与年龄无相关关系;无论BMI高低,其VSR均明显高于欧美肥胖人群和我国肥胖人群;内脏型肥胖的HbA1 c、TG、FFA水平高于皮下型肥胖组,FIns、FPG水平低于皮下型肥胖组,差异有统计学意义（P〈0．05）;（2）在校正年龄、糖尿病病程和BMI后,VA、SA和TAF均与FFA呈正相关,VSR与HbA1c呈正相关;（3）BMI为影响DBP、UA、Fins的独立危险因素,影响SBP、TG、HDL-C的重要因素;TAF是影响2hFFA的独立危险因素;VA为影响FFA的独立危险因素;SA是影响FPG的独立危险因素;VSR是影响HbA1 c的独立危险因素。结论男性T2DM患者体脂分布以中心性肥胖、尤其是腹部内脏脂肪增加为特点;其心血管危险因素不仅与总体脂有关,更与体脂分布（腹型肥胖）有关。     

肠促胰素在2型糖尿病治疗中的作用

肠促胰素是经食物刺激后由肠道细胞分泌入血、具有促进胰岛素分泌作用的一类激素;人体中,胰升糖素样肽1(GLP-1)和糖依赖性胰岛素释放肽(GIP)发挥肠促胰素效应.根据近期发表的研究,本文回顾了肠促胰素的生理作用,同时阐述了 GIP和GLP-1在2型糖尿病治疗中的特点.     

Muscle adiposity and body fat distribution in type 1 and type 2 diabetes: varying relationships according to diabetes type

OBJECTIVE: To compare the relationships between markers of total and regional adiposity with muscle fat infiltration in type 1 diabetic and type 2 diabetic subjects and their respective nondiabetic controls, and to document these relationships in type 1 diabetic subjects. DESIGN: Cross-sectional study. SUBJECTS: In total, 86 healthy, with type 1 diabetes, type 2 diabetes or control subjects. Each diabetic group was matched for age, sex and body mass index with its respective nondiabetic control group. MEASUREMENTS: Measures of body composition (hydrodensitometry), fat distribution (waist circumference, abdominal and mid-thigh computed tomography scans) and blood lipid profiles were assessed. RESULTS: Low attenuation mid-thigh muscle surface correlated similarly with markers of adiposity and body composition in all groups, regardless of diabetes status, except for visceral adipose tissue and waist circumference. Indeed, relationships between visceral adiposity and muscle adiposity were significantly stronger in type 2 vs type 1 diabetic subjects (P<0.05 for comparison of slopes). In addition, in well-controlled type 1 diabetic subjects (mean HbA(1c) of 6.8%), daily insulin requirements tended to correlate with low attenuation mid-thigh muscle surface, a specific component of fat-rich muscle (r=0.36, P=0.08), but not with glycemic control (HbA(1c)). CONCLUSION: This study suggests that the relationship of central adiposity and muscle adiposity is modulated by diabetes status and is stronger in the insulin resistant diabetes type (type 2 diabetes). In well-controlled nonobese type 1 diabetic subjects, the relationship between muscle fat accumulation and insulin sensitivity was also maintained.     

Effects of the type 2 diabetes-associated PPARG P12A polymorphism on progression to diabetes and response to troglitazone

CONTEXT: The common P12A polymorphism in PPARG (a target for thiazolidinedione medications) has been consistently associated with type 2 diabetes. OBJECTIVE: We examined whether PPARG P12A affects progression from impaired glucose tolerance to diabetes, or responses to preventive interventions (lifestyle, metformin, or troglitazone vs. placebo). PATIENTS: This study included 3548 Diabetes Prevention Program participants. DESIGN: We performed Cox regression analysis using genotype at PPARG P12A, intervention, and their interactions as predictors of diabetes incidence. We also genotyped five other PPARG variants implicated in the response to troglitazone and assessed their effect on insulin sensitivity at 1 yr. RESULTS: Consistent with prior cross-sectional studies, P/P homozygotes at PPARG P12A appeared more likely to develop diabetes than alanine carriers (hazard ratio, 1.24; 95% confidence interval, 0.99-1.57; P=0.07) with no interaction of genotype with intervention. There was a significant interaction of genotype with body mass index and waist circumference (P=0.03 and 0.002, respectively) with the alanine allele conferring less protection in more obese individuals. Neither PPARG P12A nor five other variants significantly affected the impact of troglitazone on insulin sensitivity in 340 participants at 1 yr. CONCLUSIONS: The proline allele at PPARG P12A increases risk for diabetes in persons with impaired glucose tolerance, an effect modified by body mass index. In addition, PPARG P12A has little or no effect on the beneficial response to troglitazone.     

中年男性2型糖尿病不同体型患者性激素与体脂分布的相关性分析

目的 分析中年男性2型糖尿病不同体型患者性激素水平与体脂分布的相关性.方法 选择2018-05～2019-11广西壮族自治区人民医院内分泌代谢科收治的中年男性2型糖尿病患者50例,根据体质量指数(BMI)将其分为体重正常组(A组,BMI=18.5～23.9 kg/m2,n=14),超重组(B组,24.0～27.9 kg...     

2型糖尿病患者腹部脂肪分布与糖尿病并发症的相关性研究

目的探讨2型糖尿病患者腹部脂肪分布与糖脂代谢及糖尿病并发症的关系。方法选本院内分泌科住院的2型糖尿病患者357例,定量CT测量内脏脂肪(VAT)和皮下脂肪(SAT)面积,同时检查患者糖尿病肾病、视网膜病变、周围神经病变、外周动脉粥样硬化、心脑血管疾病的患病情况。根据VAT的值以三分位数法分为3组:T1组(VAT<162.0 cm^2)、T2组(162.0≤VAT<221.1 cm^2)、T3组(VAT≥221.1 cm^2)。结果T1组HbA1C水平高于T3组(P<0.05);T1组高密度脂蛋白胆固醇(HDL-C)、肾小球滤过率(eGFR)高于T2、T3组(P<0.05);T2、T3组男性比例、年龄、体重指数(BMI)、收缩压、舒张压、三酰甘油(TG)、24h尿白蛋白、糖尿病肾病和外周动脉粥样硬化的比例高于T1组(P<0.05);T3组空腹C肽(FCP)、改良稳态模型评估的胰岛素抵抗指数(HOMA-IR)高于T1、T2组(P<0.01)。Spearman相关分析显示,VAT、SAT与BMI、FCP、HOMA-IR呈正相关(P<0.01),VAT与年龄、收缩压、舒张压、TG、24h尿白蛋白、糖尿病肾病、外周动脉粥样硬化、心脑血管疾病呈正相关(P<0.05),与HbA1C、HDL-C、eGFR呈负相关(P<0.05),SAT与总胆固醇、低密度脂蛋白胆固醇呈正相关(P<0.01),与外周动脉粥样硬化呈负相关(P<0.01)。多因素相关分析显示,校正年龄、BMI、收缩压、空腹血糖等因素后,VAT仍是发生糖尿病肾病的危险因素(P=0.013)。结论VAT、SAT均与血脂和胰岛素抵抗相关,VAT可能是2型糖尿病患者发生糖尿病肾病的危险因素。     

二甲双胍和吡格列酮对男性2型糖尿病患者骨代谢指标的影响

目的了解二甲双胍和吡格列酮对男性2型糖尿病患者骨代谢指标的影响。方法将口服降糖治疗的90例男性2型糖尿病患者随机分为格列吡嗪组、格列吡嗪＋二甲双胍组和格列吡嗪＋吡格列酮组3组,治疗1年。治疗前后检测患者的空腹血糖（FBS）、空腹胰岛素（Ins）、糖化血红蛋白（HbAlc）、骨钙素、尿吡啶酚／尿肌酐（尿PYD／Cr）。采用双能x线骨密度测量仪测量腰椎、髋部骨密度。结果二甲双胍组腰椎骨密度平均增加0．49％,髋部骨密度平均增加1．82％。而吡格列酮组腰椎、髋部骨密度分别下降1．46％和1．97％左右。治疗后二甲双胍组髋部骨密度明显高于吡格列酮组。结论与吡格列酮组比较,二甲双胍能明显增加男性糖尿病患者髋部骨密度。     

Improvement by the insulin-sensitizing agent, troglitazone, of abnormal fibrinolysis in type 2 diabetes mellitus

This study evaluated abnormal fibrinolysis in diabetic patients in terms of the pathophysiological significance and reversibility by oral hypoglycemic agents. Forty-seven patients with type 2 diabetes mellitus were randomly treated for 4 weeks with glibenclamide (n = 23) or troglitazone (n = 24). Before and after treatment, glycemic control, steady-state plasma glucose and insulin (SSPG and SSPI, respectively), and markers of fibrinolysis (tissue plasminogen activator [tPA] and plasminogen activator inhibitor-1 [PAI-1]) were analyzed in each patient. Pretreatment plasma PAI-1 in diabetic patients, but not tPA, was well correlated with the severity of retinopathy assessed by the fluorescence technique. Four weeks of treatment with troglitazone significantly decreased hemoglobin A1c (HbA1c), SSPG, and PAI-1 without an alteration of tPA. The troglitazone-induced decrease in plasma PAI-1 (50.3 v28.8 micromol/L; P < .05) was correlated with HbA1c (8.80% v7.21%, r = .539, P < .01) and SSPG (16.2 v 8.97 mmol/L, r = .562, P < .01) but not with SSPI. In contrast, treatment with glibenclamide for 4 weeks also reduced the HbA1c titer to almost the same extent as troglitazone (1.38% v 1.59%), but did not change the plasma PAI-1 or SSPG titer. These results suggest that an abnormal fibrinolytic state, especially overproduction of PAI-1, may be a pathogenic factor in the development of diabetic complications such as retinopathy, which may be improved by correction of the insulin resistance with troglitazone.     

Exercise capacity in relation to body fat distribution and muscle fibre distribution in elderly male subjects with impaired glucose tolerance, type 2 diabetes and matched controls

Background

The aim of this study was to examine the impact of insulin sensitivity and muscle fibre composition to exercise capacity in individuals with type 2 diabetes (T2D), impaired glucose tolerance (IGT) and normal glucose tolerance (NGT).

Methods

Thirty-nine male patients with T2D, 44 male subjects with IGT and 58 subjects with NGT matched for age, weight and body mass index (BMI) participated in the study. Insulin sensitivity was obtained with hyperinsulinemic-euglycemic clamps, muscle fibre distribution with a biopsy and exercise capacity from an incremental exercise test. Anthropometric measurements as height, weight, waist and hip circumference were performed.

Results

There were small differences between groups in waist hip ratio (WHR) with significance attained between NGT and T2D. There was a progressive reduction in exercise capacity, both expressed as VO_2peak and work rate from subjects with NGT to IGT to T2D. Multiple regression analysis with VO_2peak as dependent variable showed insulin sensitivity to be the most important factor followed by Type I fibres. WHR and capillary density also influenced the variance of VO_2peak.

Conclusion

Exercise capacity is independently related to insulin sensitivity, muscle fibre composition and WHR in subjects with NGT, IGT and T2D who are matched for age and BMI.     

血清二肽基肽酶4与2型糖尿病患者体脂含量及分布的关系探讨

目的 探讨2型糖尿病（T2DM）患者血清二肽基肽酶4（DPP-Ⅳ）水平与体脂含量及分布的关系.方法 选取2013年7月至11月入住云南省第一人民医院内分泌科的T2DM患者共40例为研究对象,测量其身高、体重,计算体质指数（BMI）;电化学发光法测定总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）;酶联免疫法测定DPP-Ⅳ水平;双能X线骨密度分析仪（DEXA）测定体脂及瘦肉组织含量.将所有患者分为：体重正常组（NC组）14例（BMI 18.5～24.0 kg/m^2）,超重/肥胖组（OB组）26例（BMI≥24.0 kg/m2）.组间比较采用t检验,相关性分析采用Spearman法.结果 与NC组比较,OB组血清DPP-Ⅳ水平显著升高[（765±72）比（706±91） μg/L,t=2.2480,P＜0.05].血清DPP-Ⅳ水平与全身脂肪含量（FAT）之间呈正相关（r=0.498,P＜0.05）.血清DPP-Ⅳ水平与T2DM患者躯干脂肪含量、上肢脂肪含量及下肢脂肪含量呈正相关（r=0.567、0.391、0.344,均P＜0.05）,与全身及各部位瘦肉组织含量无相关关系.结论 血清DPP-Ⅳ水平可能与T2DM患者体脂含量及分布相关.     

Relationships between cardiorespiratory fitness,metabolic control,and fat distribution in type 2 diabetes subjects

Factors contributing to the reduced cardiorespiratory fitness typical of sedentary subjects with type 2 diabetes are still largely unknown. In this study, we assessed the relationships between cardiorespiratory fitness and abdominal and skeletal muscle fat content in 39 untrained type 2 diabetes subjects, 27 males and 12 females (mean ± SD age 56.5 ± 7.3 year, BMI 29.4 ± 4.7 kg/m²). Peak oxygen uptake (VO_2peak) and ventilatory threshold (VO_2VT) were assessed by maximal cycle ergometer exercise test, insulin sensitivity by euglycemic–hyperinsulinemic clamp, and body composition by dual-energy X-ray absorptiometry. Magnetic resonance imaging was used to evaluate visceral, total subcutaneous (SAT), superficial (SSAT) and deep sub-depots of subcutaneous abdominal adipose tissue, and sagittal abdominal diameter (SAD), as well as femoral quadriceps skeletal muscle fat content. In univariate analysis, both VO_2peak and VO_2VT were inversely associated with BMI, total fat mass, SAT, SSAT, and sagittal abdominal diameter. VO_2peak was also inversely associated with skeletal muscle fat content. A significant direct association was observed between VO_2VT and insulin sensitivity. No associations between cardiorespiratory fitness parameters and metabolic profile data were found. In multivariable regression analysis, after adjusting for age and gender, VO_2peak was independently predicted by higher HDL cholesterol, and lower SAD and skeletal muscle fat content (R ² = 0.64, p < 0.001), whereas VO_2VT was predicted only by sagittal abdominal diameter (R ² = 0.48, p = 0.025). In conclusion, in untrained type 2 diabetes subjects, peak oxygen uptake is associated with sagittal abdominal diameter, skeletal muscle fat content, and HDL cholesterol levels. Future research should target these features in prospective intervention studies.     

Metabolic effects of visceral fat accumulation in type 2 diabetes

Visceral fat (VF) excess has been associated with decreased peripheral insulin sensitivity and has been suggested to contribute to hepatic insulin resistance. However, the mechanisms by which VF impacts on hepatic glucose metabolism and the quantitative role of VF in glycemic control have not been investigated. In the present study 63 type 2 diabetic subjects (age, 55 +/- 1 yr; fasting plasma glucose, 5.5-14.4 mmol/liter; hemoglobin A(1c), 6.1-11.7%) underwent measurement of 1) fat-free mass ((3)H(2)O technique), 2) sc and visceral abdominal fat area (magnetic resonance imaging), 3) insulin sensitivity (euglycemic insulin clamp), 4) endogenous glucose output ([(3)H]glucose infusion technique), and 5) gluconeogenesis ((2)H(2)O method). After adjustment for sex, age, body mass index, diabetes duration, ethnicity, and sc fat area, VF area was positively related to fasting hyperglycemia (partial r = 0.46; P = 0.001) as well as to hemoglobin A(1c) (partial r = 0.50; P = 0.0003). Insulin sensitivity was reciprocally related to VF independently of body mass index (partial r = 0.33; P = 0.01). In contrast, the relation of basal endogenous glucose output to VF was not statistically significant. This lack of association was explained by the fact that VF was positively associated with gluconeogenesis flux (confounder-adjusted, partial r = 0.45; P = 0.003), but was reciprocally associated with glycogenolysis (partial r = 0.31; P < 0.05). We conclude that in patients with established type 2 diabetes, VF accumulation has a significant negative impact on glycemic control through a decrease in peripheral insulin sensitivity and an enhancement of gluconeogenesis.