Insulin improves well-being for selected elderly type 2 diabetic subjects

The effects of insulin therapy on patient well-being, treatment satisfaction and mood, and on carer strain were studied in 30 elderly Type 2 diabetic patients (age 73 +/- 7 (SD) yr) in poor glycaemic control on tablet therapy. A comparison group of ten poorly controlled patients who remained on oral agents was also studied. After 4 weeks of insulin treatment, there were significant improvements in mental health, role-emotional, role-physical (all P<0.05) and vitality (P<0.01) domains of the short form health survey (SF-36), and also in the diabetes treatment and satisfaction questionnaire (DTSQ) and geriatric depression scale (both P<0.01) compared to baseline. After 12 weeks, the improvements in mental health, social functioning and vitality (P<0.01 for all domains), and in the DTSQ were sustained. Carer strain was lower at 4 weeks. No changes in outcomes were seen in the comparison group. In selected elderly Type 2 diabetic patients, insulin treatment is associated with significant improvements in well-being, treatment satisfaction and mood, even without significant improvements in glycaemic control and without increase in carer strain. The SF-36 and DTSQ are sensitive to the benefits of the changes in the treatment for these patients.     

老年糖尿病患者的胰岛功能变化

目的　探讨年龄对老年糖尿病患者胰岛分泌功能的影响。方法　 2型糖尿病患者 61 0例 ,按年龄分为 4组 :A组 <44岁 ;B组 45～ 59岁 ;C组 60～ 74岁 ;D组 75岁。并收集同期 NGT和 IGT患者共 1 92例作为对照。结果　 (1 )方差分析显示 ,随年龄增加老年糖尿病患者的体重、BMI、PINS、HOMA- IS明显增加 ,FBG、PBG、Hb A1 c显著降低 ,而 FINS、HOMA- IR、IAI各年龄组间差异无显著性。 (2 )协方差分析表明 ,仅控制 FBG的影响时 ,糖尿病患者各年龄组的 HOMA- IS仍有显著性差异 ,老年糖尿病患者的 HOMA- IS明显增加 ,而控制 BMI的影响后 ,各年龄组 HOMA- IS差异无显著性。 (3)糖尿病病程对 FINS、PINS、HOMA- IS的影响未达到显著性水平。 (4)决定 FINS的主要变量是 BMI,决定 PINS的主要变量是 BMI和 PBG。结论　老年糖尿病患者的胰岛素分泌功能主要决定于 BMI。年龄和糖尿病病程虽然对胰岛素分泌有负性影响但作用较弱 ,因此表现为伴随增龄的 BMI逐渐增加 ,胰岛素分泌功能也逐渐加强。校正 BMI的影响后 ,胰岛素分泌功能与年龄的关系不明显 ,但随糖尿病病程延长而逐渐减弱。     

Determinants of insulin secretion and sensitivity in bangladeshi type 2 diabetic subjects

Background: The relative contribution of insulin secretion and sensitivity in the development of type 2 diabetes mellitus (T2DM) vary from population to population due to the heterogeneous nature of the disease. The study was undertaken to evaluate the insulin secretory capacity and sensitivity in a Bangladeshi type 2 diabetic population and to explore the association of some of the anthropometric (BMI, WHR, MBP) and biochemical factors (glucose, lipids, HbA(1c)) known to modulate B-cell function and insulin action. Methods: Ninety three T2DM and 70 age-matched control subjects were studied for their fasting glucose, lipids, HbA(1c) (by HPLC) and C-peptide (by ELISA). Insulin secretion (HOMA B) and insulin sensitivity (HOMA S) were calculated by homeostasis model assessment (HOMA). Results: Both insulin secretion and sensitivity were significantly reduced in diabetic as compared to control subjects (HOMA B%, geometric M +/- SD, 34.67 +/- 1.73 vs 104.71 +/- 1.34, p < 0.001; HOMA S%, 67.60 +/- 1.69 vs 85.11 +/- 1.54, p < 0.01). However, the discriminant function coefficient for HOMA B (1.142) was about 1.5 times higher than that for HOMA S (0.731). In T2DM, HOMA B had positive correlation with BMI (r = 0.362, p < 0.001) and inverse correlation with plasma glucose (r = - 0.701, p < 0.001) and HbA1c (r = - 0.612, p < 0.001). HOMA S was inversely correlated to BMI (r = - 0.274, p < 0.01), WHR (r = - 0.252, p < 0.05), plasma total cholesterol (r = - 0.240, p < 0.05) and triglycerides (r = 0.301, p < 0.01). Conclusions: Both insulin secretory dysfunction and insulin resistance are present in Bangladeshi T2DM subjects, but B-cell dysfunction seems to be the predominant defect. BMI, plasma glucose and insulin are the major determinants of insulin secretory capacity; and generalized as well as central obesity, plasma glucose, total cholesterol, triglycerides and insulin are among the major determinants of insulin sensitivity in this population.     

Glucagon-like peptide-1 response to acarbose in elderly type 2 diabetic subjects

The anti-hyperglycemic effect of alpha-glucosidase inhibitors (AGI) is partly attributed to their ability to stimulate the secretion of glucagon-like peptide-1 (GLP-1), a gut hormone with insulin stimulating capability. To determine if this mechanism of action contributes significantly to the therapeutic efficacy of AGI in the elderly, 10 type 2 diabetic subjects over the age of 65 years were given a standardized test meal with or without 25, 50, or 100 mg acarbose. The serum glucose, insulin, triglycerides and GLP-1 levels were measured at baseline and at 1 and 2 h postprandially. The anti-hyperglycemic effect of acarbose was maximal at 25-mg dose under these experimental conditions. Serum postprandial insulin and triglycerides levels were not significantly altered with acarbose treatment. The postprandial serum GLP-1 levels rose significantly only in two subjects and only during treatment with 100-mg acarbose. There were no significant correlations between serum GLP-1 and serum glucose or insulin levels. It is concluded that in most elderly type 2 diabetic subjects, maximal anti-hyperglycemic effects can be achieved with relatively small doses of acarbose and that GLP-1 is unlikely to contribute to the clinical efficacy of this agent in this subgroup of subjects.     

Effects of metformin treatment on erythrocyte insulin binding in normal weight subjects, in obese non diabetic subjects, in type 1 and type 2 diabetic patients

We have evaluated the effects of metformin administration on erythrocyte insulin receptors in 21 subjects: 5 normal weight subjects, 5 obese non diabetics, 5 insulin-dependent diabetics (Type I) and 6 obese non insulin-dependent (Type II) diabetics. Plasma glucose, plasma insulin and erythrocyte insulin receptors were studied after 15 days of metformin (850 mg, t.d.) or placebo administered in a double blind random order. Maximum specific insulin binding to erythrocytes increased after metformin in the normals (p less than 0.01), in the obese non diabetics (p less than 0.01) and in the obese Type 2 diabetics (p less than 0.005), but not in Type I diabetics. Scatchard analysis showed that the receptor number per cell increased by 37% in the normals, by 17% in the obese non diabetics and by 182% in Type 2 diabetics. Receptor affinity increased in obese subjects but did not increase in normals and in diabetics. Only in Type II diabetics was there a significant decrease in plasma glucose. Metformin, thus, increased binding in normals by moderately increasing the capacity of cell receptors, in obese non diabetics by increasing the affinity, whereas in obese Type II diabetics it dramatically increases receptor capacity. This is consistent with the fact that metformin has a hypoglycaemic effect mainly in Type II diabetics, but not in non diabetics (whether obese or not), and could be due to a direct effect on the cell membrane.     

老年2型糖尿病患者胰岛素泵的临床应用

目的 探讨连续皮下胰岛素输注(CSII)在老年2型糖尿病患者中的应用. 方法 老年组415例,非老年组461例,均进行短期CSII强化治疗,比较两组应用CSII的差别和低血糖发生率. 结果 老年组和非老年组血糖达标时间分别为(6.3±2.1)d和(6.8±2.6)d.胰岛素日用量分别为(0.63±0.24)U/kg和(0.69±0.25)U/kg,差异均无统计学意义;老年组夜间基础率较低,且夜间低血糖发生率较高.分别为0.08次/例和0.04次/例. 结论 CSII能有效控制老年2型糖尿病患者的血糖,但应注意减少晚餐前大剂量和夜间的基础率,从而降低低血糖风险.     

老年2型糖尿病患者胰岛素抵抗程度与骨骼肌量的相关性

目的探究老年2型糖尿病(T2DM)患者胰岛素抵抗(IR)程度与骨骼肌量的相关性。方法选择2018年4月至2019年8月南京医科大学附属南京医院老年T2MD患者83例,根据是否合并肌肉减少症将患者分为2组,对照组为不合并肌肉减少症患者51例,研究组为合并肌肉减少症患者32例。比较2组患者的基本资料、血脂指标、血糖以及胰岛素抵抗指标。采用SPSS 19.0软件进行数据分析。根据数据类型,组间比较分别采用χ2检验或t检验。通过logistic回归分析T2DM患者骨骼肌量减少的危险因素。结果研究组患者的年龄显著高于对照组,体质量指数显著低于对照组(P<0.05)。研究组患者的稳态模型胰岛β细胞功能指数(HOMA-β)显著低于对照组,而稳态模型胰岛素抵抗指数(HOMA-IR)显著高于对照组(P<0.05)。T2DM患者四肢骨骼肌质量指数(ASMI)数值与HOMA-β呈正相关(r=0.441,P<0.05),与HOMA-IR呈负相关(r=-0.463,P<0.05)。logistic回归分析结果显示年龄及IR是引起T2DM患者骨骼肌量降低的独立危险因素(P<0.05)。结论年龄HOMA-β和HOMA-IR与T2DM患者的ASMI具有相关性,并且年龄、以及IR是引起T2DM患者肌肉减少症的独立危险因素。     

Cognitive function and brain atrophy in elderly type 2 diabetic patients in comparison with non-diabetic elderly subjects]

Previous studies have suggested that type 2 diabetic mellitus could lead to learning and memory deficits. We studied cognitive function tests and brain computed tomography (CT) findings in elderly subjects with drug-treated type 2 diabetic patients (n = 9), diet-treated type 2 diabetic patients (n = 8) and nondiabetic subjects (CR, n = 21). A battery of cognitive function tests (Cog-T; WAIS-R's digit span test and symbol test, Stroop Test, ADAS's verbal memory test, and MMSE) was carried out on two occasions, separated by at least 6 months. Brain CT was analyzed by the following 5 variables; 1) Evan's Ratio, 2) Inverse Cella Media Index, 3) maximum width of the third ventricle, 4) maximum width of temporal horn tips on both sides and 5) maximum width of the Sylvian fissure at the insula, bilaterally. The scores of Cog-T did not differ significantly between the groups. On brain CT measurements, maximum width of the temporal horn tips on right side were significantly different in the three groups (ANOVA, P = 0.035). The drug-treated diabetics subjects had wider temporal horn tips on the right side than did the diet treated diabetics and nondiabetic subjects (Fisher's post hoc test, P = 0.030, P = 0.016).     

Lipid accumulation in overweight type 2 diabetic subjects: relationships with insulin sensitivity and adipokines

Adipokines are known to play a fundamental role in the etiology of obesity, that is, in the impaired balance between increased feeding and decreased energy expenditure. While the adipokine-induced changes of insulin resistance in obese diabetic and nondiabetic subjects are well known, the possible role of fat source in modulating insulin sensitivity (IS) remains controversial. The aim of our study was to explore in overweight type 2 diabetic patients (T2DM) with metabolic syndrome IS in different energy storage conditions (basal and dynamic) for relating it to leptin and adiponectin. Sixteen T2DM (5/11 F/M; 59 ± 2 years; 29.5 ± 1.1 kg/m²) and 16 control (CNT 5/11; 54 ± 2; 29.1 ± 1.0) underwent an oral glucose tolerance test. Fasting IS was measured by QUICKI, while the dynamic one with OGIS. The insulinogenic index (IGI) described beta cell function. Also, the lipid accumulation product parameter (LAP) was assessed. LAP accounts for visceral abdominal fat and triglycerides, and it is known to be related to IS. Possible interrelationships between LAP and adipokines were explored. In T2DM and CNT, adiponectin (7.4 ± 0.5 vs. 7.8 ± 0.9 μg/mL), leptin (13.3 ± 3.0 vs. 12.4 ± 2.6 ng/mL), and QUICKI (0.33 ± 0.01 vs. 0.33 ± 0.01) were not different (P > 0.40), at variance with OGIS (317 ± 11 vs. 406 ± 13 mL/min/m²; P = 0.006) and IGI (0.029 ± 0.005 vs. 0.185 ± 0.029 × 10³ pmol_I/mmol_G; P = 0.00001). LAP was 85 ± 15 cm × mg/dL in T2DM and 74 ± 10 in CNT (P > 0.1), correlated with OGIS in all subjects (R = ?0.42, P = 0.02) and QUICKI (R = ?0.56, P = 0.025) in T2DM. Leptin correlated with QUICKI (R = ?0.45, P = 0.009), and adiponectin correlated with OGIS (R = 0.43, P = 0.015). In overweight T2DM, insulin sensitivity in basal condition appears to be multifaceted with respect to the dynamic one, because it should be more fat-related. Insulin sensitivity appears to be incompletely described by functions of fasting glucose and insulin values alone and the use of other indices, such as LAP could be suggested.     

Influence of ripeness of banana on the blood glucose and insulin response in type 2 diabetic subjects.

Banana is a popular and tasty fruit which often is restricted in the diet prescribed for diabetic patients owing to the high content of free sugars. However, in under-ripe bananas starch constitutes 80-90% of the carbohydrate content, which as the banana ripens changes into free sugars. To study the effect of ripening on the postprandial blood glucose and insulin responses to banana, 10 type 2 (non-insulin-dependent) diabetic subjects consumed three meals, consisting of 120 g under-ripe banana, 120 g over-ripe banana or 40 g white bread on separate days. The mean postprandial blood glucose response area to white bread (181 +/- 45 mmol l-1 x 240 min) was significantly higher compared with under-ripe banana (62 +/- 17 mmol l-1 x 240 min: p < 0.01) and over-ripe banana (106 +/- 17 mmol l-1 x 240 min: p < 0.01). Glycaemic indices of the under-ripe and over-ripe bananas differed (43 +/- 10 and 74 +/- 9: p < 0.01). The mean insulin response areas to the three meals were similar: 6618 +/- 1398 pmol l-1 x 240 min (white bread), 7464 +/- 1800 pmol l-1 x 240 min (under-ripe banana) and 8292 +/- 2406 pmol l-1 x 240 min (over-ripe banana). The low glycaemic response of under-ripe compared with over-ripe bananas may be ascribed to the high starch content, which has previously been found to be only hydrolysed slowly by alfa-amylase in humans.(ABSTRACT TRUNCATED AT 250 WORDS)     

替米沙坦对老年2型糖尿病肾病患者胰岛素抵抗和胰淀素分泌的影响

目的 探讨替米沙坦对老年2型糖尿病肾病患者胰岛素抵抗和胰淀素分泌的影响.方法 162例老年糖尿病肾病患者按尿蛋白排泄量(UAE)和血肌酐水平分为3组:早期肾病组、临床肾病组和肾功能减退组.每组再随机分为替米沙坦组(80 mg/d)和氯沙坦组(100 mg/d).测定治疗前后UAE、内生肌酐清除率、空腹血糖、空腹胰岛素和血胰淀素水平,计算胰岛素抵抗指数(HOMA-IR)和胰岛素敏感指数(ISI).结果 血胰淀素与UAE、空腹胰岛素、HOMA-IR呈正相关,与ISI呈负相关,与内生肌酐清除率和空腹血糖无关.替米沙坦能显著降低各期糖尿病肾病患者空腹胰岛素[(16.25±2.24)和(10.86±2.03)mIU/L,P＜0.01)]、HOMA-IR(4.16±0.42和3.07±0.28,P＜0.05)及血胰淀素水平[(27.76±4.34)和(18.21±3.03)pmol/L,P＜0.01],升高ISI.与氯沙坦各治疗组比较,差异均有统计学意义,且改善作用在早期肾病组更显著(P＜0.05).结论 替米沙坦能够改善不同分期老年2型糖尿病肾病患者胰岛素抵抗,降低血胰淀素水平,其作用优于对应剂量氯沙坦.     

A strategy for selection of elderly type 2 diabetic patients for insulin therapy, and a comparison of two insulin preparations

Sixty-six patients with secondary failure to oral hypoglycaemic therapy were assessed in hospital, and those whose fasting blood glucose concentration was greater than or equal to 10.0 mmol l-1 were treated with insulin once a day for 6 months. Only 22 patients fulfilled this criterion, and they were randomly allocated to a daily injection of either Humulin-Zn (12 patients) or Neulente insulin (10 patients). The remaining patients were considered to be noncompliant with therapy. At the end of 6 months' insulin therapy a significant (p less than 0.05) improvement occurred in HbA1c from a median (range) of 13.2(9.8-16.4)% and 13.1(10.5-16.2)% to 10.6(8-14.2)% and 11.2(8.7-13.5)% in patients given Humulin-Zn and Neulente, respectively. However, there were 46 episodes of hypoglycaemia reported by patients who received Humulin-Zn, 36 of which occurred between 0300 and 0600 h. Only four episodes were reported by the Neulente-treated group. In addition, six patients treated with Humulin-Zn (but only one patient on Neulente insulin) required the addition of short-acting insulin. The patients not treated with insulin showed a significant (p less than 0.05) improvement in blood glucose control 2 months after in-patient assessment but this improvement was not sustained to 6 months.     

Effects of short-term very low-calorie diet on intramyocellular lipid and insulin sensitivity in nondiabetic and type 2 diabetic subjects

The study aimed to analyze the effects of a short-term very low-calorie diet (VLCD) on intramyocellular lipid (IMCL), total body fat, and insulin sensitivity in a group of obese nondiabetic and type 2 diabetic subjects. Seven untreated type 2 diabetic and 5 obese nondiabetic individuals were studied before and after a 6-day VLCD using proton magnetic resonance spectroscopy to quantify IMCL, dual-energy x-ray absorptiometry to assess body fat, and hyperinsulinemic-euglycemic clamps to measure peripheral insulin sensitivity. In both groups, decrements in total body fat mass and body mass index were small but statistically significant. In contrast, the diet resulted in a pronounced reduction in IMCL compared with baseline values in nondiabetic subjects (56% decrease) and type 2 diabetic subjects (40% decrease) (P < .05), and this was accompanied by an overall 9.3% increase in maximally stimulated glucose disposal rate (P < .01). Intramyocellular lipid was significantly correlated with insulin sensitivity (r = -0.69, P < .01) and waist circumference (r = 0.72 and 0.83, baseline and postdiet, respectively; both P < .01), but neither IMCL nor insulin sensitivity was related to measures of general adiposity such as body mass index, percentage of body fat, or total body fat (P = not significant). In conclusion, short-term VLCD is accompanied by small decrements in general adiposity, marked decrease in IMCL, and an increase in insulin sensitivity in nondiabetic and type 2 diabetic subjects. Therefore, rapid amelioration of insulin resistance by VLCD can be partially explained by loss of IMCL both in nondiabetic and type 2 diabetic subjects in the absence of substantial changes in total body fat. These observations are consistent with the idea that insulin resistance is more directly related to IMCL rather than to body fat per se.     

A randomised,controlled trial of self-monitoring of blood glucose in patients with type 2 diabetes receiving conventional insulin treatment

Aims/hypothesis

We evaluated whether self-monitoring of blood glucose (SMBG) leads to better glycaemic control (HbA_1c) in patients with type 2 diabetes on conventional insulin regimens.

Methods

Patients with type 2 diabetes on a conventional insulin regimen (basal or premixed insulin with or without additional oral glucose-lowering agents) were recruited at study centres led by members of the German Diabetes Association. In a randomised, prospective, open 2?×?2 factorial design, the once-weekly performance of four-point glucose profiles (SMBG +; n?=?151 patients) was compared with no SMBG (SMBG ?; n?=?149), and the measuring and transmitting of HbA_1c results to the study centres (HbA_1c +; n?=?158, of these 82 SMBG ? and 76 SMBG +) was compared with HbA_1c measurement without disclosure of results (HbA_1c ?; n?=?142, of these 67 SMBG ? and 75 SMBG +). Randomised allocation was carried out by a central office, using sequentially numbered, sealed envelopes. The primary endpoint was the reduction of HbA_1c compared with baseline after 12 months. Secondary analyses were of therapy intensification in response to higher blood or urinary glucose or HbA_1c. Participants and caregivers were not blinded as to the allocation of interventions, whereas the laboratory determining HbA_1c remained blinded.

Results

Patient characteristics were balanced across groups. A total of 56 patients dropped out. In completers, HbA_1c was reduced in the SMBG + group from 7.3% to 7.0%, i.e. by 0.3% (0.1%, 0.5%) vs SMBG ? from 7.3% to 7.0% and 0.3% (0.2%, 0.5%), respectively, the difference being 0.0% (?0.2%, 0.2%) (p?=?0.93). The disclosure of HbA_1c results had no significant influence, with a difference of 0.1% (?0.1%, 0.4%) (p?=?0.28). Values above are mean (95% CI). The ORs for therapy intensification significantly rose as the following increased: proportions of urine samples testing positive for glucose, HbA_1c concentrations, and fasting or postprandial glucose concentrations. No important adverse events were associated with the interventions.

Conclusions/interpretation

SMBG profiles once weekly or the disclosure of HbA_1c results did not improve glycaemic control in patients with type 2 diabetes on conventional insulin treatment, although indicators of hyperglycaemia increased the likelihood of therapy intensification. Greater intensification may be necessary to impact on glycaemic control.

Trial registration:

www.clinicaltrials.gov (registration code NCT00688363)

Funding:

Deutsche Diabetes-Gesellschaft, Deutsche Diabetes-Stiftung, Bayer Vital GmbH     

A comparison of insulin aspart and regular insulin in elderly patients with type 2 diabetes

AIM: To evaluate the pharmacokinetic and pharmacodynamic properties of insulin aspart in elderly patients with diabetes. METHODS: Studies were conducted in elderly patients with diabetes (n = 19, M/F 10/9, age 72 +/- 1 years, BMI 27 +/- 1 kg/m(2), HbA(1c) 6.4 +/- 0.1%, diabetes duration < 5 years). Nine patients were treated with metformin, and ten with diet. Subjects underwent 2 studies in random order. In one study, 0.1 u/kg of novolin R (Novo Nordisk, Copenhagen, Denmark) was administered at 7:30 am. Thirty minutes later, at time 0, subjects were given 235 ml of ensure with fibre. The other study was identical to the first except that insulin aspart (Novorapid, Novo Nordisk, Copenhagen, Denmark) 0.1 u/kg was given at time zero. Insulin and glucose valuves were measured as at regular intervals. RESULTS: Insulin and glucose profiles were nearly identical with insulin aspart and regular human insulin. The AUC for glucose (aspart: 6.9 +/- 0.1 mM; regular: 7.1 +/- 0.1 mM, p = ns) and insulin (aspart: 335 +/- 30 pM; regular: 330 +/- 25 pM, p = ns) did not differ between groups. CONCLUSIONS: Insulin aspart appears to act similarly to regular human insulin in elderly patients with type 2 diabetes.     

Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects

BACKGROUND AND AIMS: Abdominal fat accumulation (visceral/hepatic) has been associated with hepatic insulin resistance (IR) in obesity and type 2 diabetes (T2DM). We examined the relationship between visceral/hepatic fat accumulation and hepatic IR/accelerated gluconeogenesis (GNG). METHODS: In 14 normal glucose tolerant (NGT) (body mass index [BMI] = 25 +/- 1 kg/m(2)) and 43 T2DM (24 nonobese, BMI = 26 +/- 1; 19 obese, BMI = 32 +/- 1 kg/m(2)) subjects, we measured endogenous (hepatic) glucose production (3-(3)H-glucose) and GNG ((2)H(2)O) in the basal state and during 240 pmol/m(2)/min euglycemic-hyperinsulinemic clamp, and liver (LF) subcutaneous (SAT)/visceral (VAT) fat content by magnetic resonance spectroscopy/magnetic resonance imaging. RESULTS: LF was increased in lean T2DM compared with lean NGT (18% +/- 3% vs 9% +/- 2%, P < .03), but was similar in lean T2DM and obese T2DM (18% +/- 3% vs 22% +/- 3%; P = NS). Both VAT and SAT increased progressively from lean NGT to lean T2DM to obese T2DM. T2DM had increased basal endogenous glucose production (EGP) (NGT, 15.1 +/- 0.5; lean T2DM, 16.3 +/- 0.4; obese T2DM, 17.2 +/- 0.6 micromol/min/kg(ffm); P = .02) and basal GNG flux (NGT, 8.6 +/- 0.4; lean T2DM, 9.6 +/- 0.4; obese T2DM, 11.1 +/- 0.6 micromol/min/kg(ffm); P = .02). Basal hepatic IR index (EGP x fasting plasma insulin) was increased in T2DM (NGT, 816 +/- 54; lean T2DM, 1252 +/- 164; obese T2DM, 1810 +/- 210; P = .007). In T2DM, after accounting for age, sex, and BMI, both LF and VAT, but not SAT, were correlated significantly (P < .05) with basal hepatic IR and residual EGP during insulin clamp. Basal percentage of GNG and GNG flux were correlated positively with VAT (P < .05), but not with LF. LF, but not VAT, was correlated with fasting insulin, insulin-stimulated glucose disposal, and impaired FFA suppression by insulin (all P < .05). CONCLUSIONS: Abdominal adiposity significantly affects both lipid (FFA) and glucose metabolism. Excess VAT primarily increases GNG flux. Both VAT and LF are associated with hepatic IR.     

Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects

OBJECTIVES: The aim of this study was to examine if an acute nicotine infusion alters insulin sensitivity to a similar degree in type 2 diabetic patients as in healthy control subjects. DESIGN: . Double-blind, cross-over, placebo-controlled, randomized experimental study. Nicotine 0.3 microg kg-1 min(-1) or NaCl was infused (2 h) during a euglycaemic hyperinsulinaemic clamp (4 h) to assess insulin sensitivity. SETTING: University research laboratory. SUBJECTS: Six male and female type 2 diabetic patients [DM2; age 54 +/- 10 (mean +/- SD) years; body mass index (BMI) 25.6 +/- 2.9 kg m(-2)] treated with diet or one oral hypoglycaemic agent and six age- and BMI-matched control subjects (Ctr). MAIN OUTCOME MEASURE: Insulin sensitivity (rate of glucose infusion per kg fat free body mass and minute), nicotine and free fatty acid (FFA) levels, pulse rate and blood pressure. RESULTS: The infusions produced similar nicotine levels in both groups. In the absence of nicotine, DM2 were more insulin resistant than Ctr (6.7 +/- 0.4 vs. 10.9 +/- 0.3 mg kg-1 LBM min(-1), respectively; P < 0.0001). This insulin resistance was further aggravated by the nicotine infusion in DM2 but not in Ctr (4.6 +/- 0.3 vs. 10.9 +/- 0.3 mg kg(-1) LBM min(-1); P < 0.0001). Only minor differences were seen in FFA levels, pulse rates and blood pressure. CONCLUSIONS: At this low infusion rate, nicotine aggravated the insulin resistance in DM2 but not in Ctr. This finding may be because of the (dysmetabolic) diabetic state per se or to an increased sensitivity to environmental factors associated with a genetic predisposition for type 2 diabetes. These results show that diabetic subjects are particularly susceptible to the detrimental effects of nicotine.     

A randomised controlled trial of the effect of low fat diet advice on dietary response in insulin independent diabetic women

Summary Type 2 (insulin independent) diabetic women were randomly allocated to receive advice for low fat diets or low carbohydrate diets. By 24 h weighed dietary intakes before and after a mean interval of six months, patients in the low fat group had reduced their fat intake from 41% to 31% of total energy, while carbohydrate percentage of total energy intake increased from 38% to 46%. Percentage energy intake from fat and carbohydrate in the control group remained unchanged. Body weight fell in both groups, especially for patients in the low fat group who were obese (weight/height2 28 kg/m²). Mean plasma glucose, HbA₁, and triglycerides were unchanged. Mean plasma total cholesterol fell significantly in the low fat group compared with the controls (p < 0.001), but there was no significant difference in the small reduction of high density lipoprotein cholesterol observed in both groups. Thus, adherence to low fat diets occurred without deterioration of diabetes and with benefit for weight and total cholesterol.     

Efficacy of glimepiride in Japanese type 2 diabetic subjects

We investigated the efficacy of glimepiride, a third-generation sulfonylurea (SU), in Japanese type 2 diabetic patients in whom glycemic control had been inadequate with a conventional SU, gliclazide or glibenclamide. A total of 172 Japanese type 2 diabetic patients (HbA1C > or = 7.0%), maintained on a conventional SU, were randomly assigned to the 3rd SU group (SU treatments switched to glimepiride) or the 2nd SU group (treatments not changed). The conventional SU was switched to the indicated doses of glimepiride (gliclazide 40 mg = glimepiride 1 mg, glibenclamide 2.5 mg = glimepiride 2 mg). After 6 months, glycemic control (HbA1C and fasting plasma glucose) had not changed significantly in either the 2nd or the 3rd SU group. The homeostasis assessment model of insulin resistance (HOMA-IR) in the 3rd SU group was decreased by more than 10% (p = 0.015), whereas no change was observed in the 2nd SU group. The triglyceride level was decreased by approximately 10% in the 3rd SU group, not a significant change (p = 0.080). Patients who had been treated with only SU, or treated with SU for a short time (less than 5 years), and who were also obese (BMI > or = 25) or had a high HOMA-IR (HOMA-IR > or = 3), showed significantly reduced insulin resistance. According to logistic regression analysis, high BMI ( > or = 25) was the only variable predicting that glimepiride would more effectively improve HbA1C than conventional SU treatment. In conclusion, switching conventional SUs to glimepiride reduced insulin resistance without improving glycemic control. A notable finding of this study is that glimepiride was more beneficial in obese than in non-obese Japanese type 2 diabetic patients.