Starting insulin in type 2 diabetes: continue oral hypoglycemic agents? A randomized trial in primary care

OBJECTIVE: To evaluate the effects of insulin 30/70 twice daily or bedtime isophane (NPH) insulin plus continued sulfonylurea and metformin in patients with type 2 diabetes in primary care. STUDY DESIGN: Open-label, randomized trial. POPULATION: Persons younger than 76 years with type 2 diabetes whose disease had not been controlled with oral hypoglycemic agents alone. A total of 64 insulin-naive patients treated with maximal feasible dosages of sulfonylurea and metformin (baseline glycosylated hemoglobin [HbA1c]=8.5%) were randomly assigned to insulin monotherapy (IM group; n=31) or insulin in addition to unchanged oral hypoglycemic medication (IC group; n=33) for 12 months. Insulin doses were adjusted to obtain fasting glucose <7.0 mmol/L and postprandial glucose <10.0 mmol/L. OUTCOMES MEASURED: Outcome measures included HbA1c, treatment failure, weight, hypoglycemic events and symptoms, satisfaction with treatment, general well-being, and fear of injecting insulin and testing. RESULTS: HbA1c improved from 8.3% to 7.6% in the IC group, and from 8.8% to 7.6% in the IM group (P=NS). The IC group had 24% treatment failures, compared with 2% in the IM group (P=.09). Patients in the IC group had less weight gain than those in the IM group (1.3 vs 4.2 kg; P=.01), and they reported fewer hypoglycemic events (2.7 vs 4.3; P=.02). Increased satisfaction with treatment was equal in the 2 groups, and general well-being improved by 3.0 points more in the IC group (P=.05). Fear of self-injecting and self-testing did not differ. CONCLUSIONS: Bedtime NPH insulin added to maximal therapy with sulfonylurea and metformin is an effective, simple, well-tolerated approach for patients with uncontrolled type 2 diabetes.     

不同药物对新诊断2型糖尿病患者控制血糖的疗效观察

目的:观察不同药物对新诊断2型糖尿病患者的疗效。方法:102例新诊断的2型糖尿病患者随机分为艾塞那肽组(34例)、胰岛素组(34例)和二甲双胍组(34例)。三组患者治疗周期均为16周。分别于治疗前、治疗8周及16周测量糖化血红蛋白(HbAlc)、空腹血糖(FPG)、餐后2 h血糖(2h-PG),低血糖发生率、体重变化情况。结果:三组患者经治疗8周和16周时HbAlc、FPG和2h-PG均降低(P<0.05或0.01),并且艾塞那肽组及胰岛素组血糖下降与二甲双胍组相比差别有统计学意义(P<0.05或0.01)。结论:三种药物对新诊断2型糖尿病患者血糖均能控制良好,艾塞那肽注射液及胰岛素的降糖效果优于二甲双胍,艾塞那肽注射液及二甲双胍减重效果优于胰岛素。     

Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin

Inhibition of dipeptidyl peptidase-4 (DPP-4) as a novel therapy for type 2 diabetes is based on prevention of the inactivation process of bioactive peptides, the most important in the context of treatment of diabetes of which is glucagon-like peptide-1 (GLP-1). Most clinical experience with DPP-4 inhibition is based on vildagliptin (GalvusR, Novartis) and sitagliptin (JanuviaR, Merck). These compounds improve glycemic control both in monotherapy and in combination with other oral hyperglycemic agents. Both have also been shown to efficiently improve glycemic control when added to ongoing metformin therapy in patients with inadequate glycemic control. Under that condition, they reduce HbA1C levels by 0.65%-1.1% (baseline HbA1C 7.2-8.7%) in studies up to 52 weeks of duration in combination versus continuous therapy with metformin alone. Sitagliptin has also been examined in initial combination therapy with metformin have; HbA1 was reduced by this combination by 2.1% (baseline HbA1C 8.8%) after 24 weeks of treatment. Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1. The combination of DPP-4 inhibition and metformin has been shown to be highly tolerable with very low risk of hypoglycemia. Hence, DPP-4 inhibition in combination with metformin is an efficient, safe and tolerable combination therapy for type 2 diabetes.     

Clearance and action of insulin during general or epidural anaesthesia

Surgery performed under general anaesthesia induces impaired glucose tolerance together with comparatively low levels of insulin. This contrasts with the normal glucose tolerance and normal insulin levels found in patients operated upon under epidural anaesthesia. The aim of this study was to investigate insulin clearance and insulin action during surgery. Sixteen non-diabetic patients admitted for elective inguinal herniorrhaphy were operated under general anaesthesia (thiopentone, N(2)O/O(2) (2 1 ), fentanyl, pancuronium bromide) or after high epidural blockade with mepivacaine. The clearance and hypoglycemic action of insulin were determined after a 2.5 min infusion of a physiologic dose of insulin. All patients were studied the day before operation and during surgery. The hypoglycemic action of insulin, expressed as % decrement from the pre-test blood glucose level, was unchanged during epidural anaesthesia but reduced during general anaesthesia (22.4 +/- 1.8% pre-operatively vs 7.5 +/- 1.3% intra-operatively, p < 0.01). The insulin resistance during general anaesthesia was associated with a decreased clearance of insulin (20.3 +/- 0.8 ml min(-1) kg(-1) pre-operatively vs 12.7 +/- 1.1 ml min(-1) kg(-1) intra-operatively, p < 0.01), whereas insulin clearance was normal during epidural anaesthesia. It is concluded that general anaesthesia, but not epidural anaesthesia, induces a reduction in both clearance and hypoglycemic action of insulin.     

Glycosylated haemoglobin and serum insulin antibodies in type I diabetes

Type 1 diabetics receiving once (Group 1, n = 72) and twice (Group 2, n = 48) daily subcutaneous injections of conventional beef insulin were compared, on a cross-sectional basis, in respect of insulin antibody binding by serum and total glycosylated haemoglobin (HbA1). Patients in Group 1 had higher insulin antibody binding (25.2 +/- 15.8% vs 17.0 +/- 13.9%; p less than 0.01) and higher HbA1 levels (12.5 +/- 2.0% vs 11.0 +/- 1.8%; p less than 0.001) than patients in Group 2. An inverse correlation (tau = -0.28, p less than 0.01) was observed between HbA1 and insulin antibody binding in C-peptide non-secretors of Group 1 but not in Group 1 C-peptide secretors, nor in C-peptide secretors and/or non-secretors of Group 2. It is suggested that in Type 1 diabetics who receive a single daily insulin injection and who have no endogenous insulin secretion, insulin antibodies may aid glycaemic control by prolonging insulin action.     

Effects of metformin and vanadium on leptin secretion from cultured rat adipocytes

OBJECTIVE: We have reported that glucose utilization regulates leptin expression and secretion from isolated rat adipocytes. In this study, we employed two antidiabetic agents that act to increase glucose uptake by peripheral tissues, metformin and vanadium, as pharmacological tools to examine the effects of altering glucose utilization on leptin secretion in primary cultures of rat adipocytes. RESEARCH METHODS AND PROCEDURES: Isolated adipocytes (100 microL of packed cells per well) were anchored in a defined matrix of basement membrane components (Matrigel) with media containing 5.5 mM glucose and incubated for 96 hours with metformin or vanadium. Leptin secretion, glucose utilization, and lactate production were assessed. RESULTS: Metformin (0.5 and 1.0 mM) increased glucose uptake in the presence of 0.16 nM insulin by 37 +/- 10% (p < 0.005) and 62 +/- 8% (p < 0.0001) over insulin alone, respectively. Metformin from 0.5 to 5.0 mM increased lactate production by 105 +/- 43% (p < 0.025) to 202 +/- 52% (p < 0.0025) and at 1.0 and 5.0 mM increased the proportional rate of glucose conversion to lactate by 78 +/- 18% (p < 0.005) and 166 +/- 41% (p < 0.0025), respectively. At concentrations less than 0.5 mM, metformin did not affect leptin secretion, but at 0.5 mM, the only concentration that significantly increased glucose utilization without increasing glucose conversion to lactate, leptin secretion was modestly stimulated (by 20 +/- 9%; p < 0.05). Concentrations from 1.0 to 25 mM inhibited leptin secretion by 25 +/- 8% (p < 0.005) to 89 +/- 4% (p < 0.0001). Across metformin doses, leptin secretion was inversely related to the percentage of glucose taken up and released as lactate (r = -0.74; p < 0.0001). Vanadium (5 to 20 microM) increased glucose uptake from 20 +/- 7% (p < 0.01) to 34 +/- 13% (p < 0.02) and increased lactate production at 5 microM by 17 +/- 8% (p < 0.025) and 10 microM by 61 +/- 20% (p < 0.02) but did not alter the conversion of glucose to lactate. Vanadium (5 to 50 microM) inhibited leptin secretion by 33 +/- 6% (p < 0.0025) to 61 +/- 8% (p < 0.0001). DISCUSSION: Both metformin and vanadium increase glucose uptake and inhibit leptin secretion from cultured adipocytes. The inhibition of leptin secretion by metformin is related to an increase in the metabolism of glucose to lactate. The inhibition by vanadium most likely involves direct effects on cellular phosphatases. We hypothesize that the effect of glucose utilization to stimulate leptin production involves the metabolism of glucose to a fate other than anaerobic lactate production, possibly oxidation or lipogenesis.     

Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet

Vildagliptin is a potent and selective inhibitor of dipeptidyl peptidase-IV (DPP-4), orally active, that improves glycemic control in patients with type 2 diabetes (T2DM) primarily by enhancing pancreatic (alpha and beta) islet function. Thus vildagliptin has been shown both to improve insulin secretion and to suppress the inappropriate glucagon secretion seen in patients with T2DM. Vildagliptin reduces HbA(1c) when given as monotherapy, without weight gain and with minimal hypoglycemia, or in combination with the most commonly prescribed classes of oral hypoglycemic drugs: metformin, a sulfonylurea, a thiazolidinedione, or insulin. Metformin, with a different mode of action not addressing beta-cell dysfunction, has been used for about 50 years and still represents the universal first line therapy of all guidelines. However, given the multiple pathophysiological abnormalities in T2DM and the progressive nature of the disease, intensification of therapy with combinations is typically required over time. Recent guidelines imply that patients will require pharmacologic combinations much earlier to attain and sustain the increasingly stringent glycemic targets, with careful drug selection to avoid unwanted adverse events, especially hypoglycemia. The combination of metformin and vildagliptin offers advantages when compared to currently used combinations with additive efficacy and complimentary mechanisms of action, since it does not increase the risk of hypoglycemia and does not promote weight gain. Therefore, by specifically combining these agents in a single tablet, there is considerable potential to achieve better blood glucose control and to improve compliance to therapy.     

不同时长运动联合二甲双胍对2型糖尿病血糖控制效果的meta分析

目的 探讨不同时长运动疗法联合二甲双胍治疗对2型糖尿病患者血糖控制的不同疗效。方法 计算机检索 PubMed、EMbase、Elsevier、CNKI、WanFang Data、Web of Science等数据库,检索相关随机对照试验（RCTs）,采用RevMan 5.3 软件进行meta分析。结果 共纳入10个 RCTs,包括974例患者。meta分析结果显示,与单纯二甲双胍治疗相比,运动疗法联合二甲双胍治疗2～3个月后,空腹血糖（FBG）显著下降（SMD = - 1.61,95%CI: - 2.68～- 0.53,P = 0.003）,糖化血红蛋白（HbA1c）明显降低（SMD = - 1.41,95%CI: - 1.75～- 1.07,P＜0.001）,空腹胰岛素（FINS）含量降低至更接近于正常范围（SMD = - 1.14,95%CI: - 2.15～- 0.13,P = 0.03）;胰岛素抵抗指数（HOMA - IR）（SMD = - 0.75,95%CI:- 1.32～- 0.18,P = 0.010）与餐后两小时血糖（2hPBG）明显降低（SMD = - 1.42,95%CI:- 2.46～- 0.39,P = 0.007）;运动疗法联合二甲双胍治疗6个月后,FBG（SMD = - 0.74,95%CI: - 1.97～0.49,P = 0.24）及2hPBG（SMD = - 1.24,95%CI: - 2.23～- 0.26,P = 0.01）的控制效果未表现出显著差异。结论 2～3个月运动联合二甲双胍治疗在控制血糖、减低胰岛素抵抗方面比单纯二甲双胍治疗效果更为显著,而干预时长延长至6个月时,运动联合二甲双胍治疗在糖尿病患者血糖控制上的叠加效应消失。由于纳入的文章数目及质量有限,上述结论还需更多高质量研究进一步论证。     

A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes

Type 2 diabetes (T2D) is a progressive disorder with a consistent and steady increase in glycosylated hemoglobin (HbA1c) over time associated with enhanced risk of micro- and macrovascular complications and a substantial reduction in life expectancy. There are three major pathophysiologic abnormalities associated with T2D: impaired insulin secretion, excessive hepatic glucose output, and insulin resistance in skeletal muscle, liver, and adipose tissue. These defects have been treated in clinical praxis by use of oral insulin secretagogues (sulfonylureas/ glinides) or insulin, biguanides, and thiazolidinediones (TZDs) respectively. Pioglitazone HCL is an insulin sensitizer in the TZD family and glimepiride is an insulin secretagogue in the SU family. This article reviews mechanisms of action and clinical data behind the use of these two commonly used oral hypoglycemic agents with documented efficacy and good safety profile of once-daily administration, alone or in combination with insulin or metformin, in the management of T2D in terms of glycemic and non-glycemic effects, tolerability and side effects, and impact on vascular health.     

Panorama de los tratamientos actuales disponibles para los pacientes con diabetes tipo 2. Algoritmo terapéutico de la ADA/EASD. Seguridad y tolerabilidad

Type 2 diabetes is defined by chronic hyperglycemia due to at least two pathogenic alterations: resistance to the action of peripheral insulin and insufficient pancreatic insulin secretion. The pharmacological treatment of hyperglycemia in type 2 diabetes should be individualized. The choice of specific oral drug (or combination of drugs) is based on the drug's physiological mechanism, the general recommendations of the clinical practice guidelines, systematic reviews and analysis of data from clinical trials and observational studies. In general terms, clinical practice guidelines recommend starting with lifestyle modifications together with metformin, either from the outset or at 3 months; the combination should be individualized depending on the patient's profile. Therapy may be intensified every 3-6 months until targets (HbA1c 6.5-7.5%) have been reached. To chose the second drug, both its efficacy (mechanism of action) and side effects (hypoglycemic episodes, effect on weight, intestinal effects, edema/cardiac insufficiency and renal or liver insufficiency) should be considered. The controversy on the safety of oral drugs and insulin is constantly reviewed. The cardiovascular safety of intensive hyperglycemia treatment in patients with type 2 diabetes, particularly with certain agents, is an open debate. Finally, the association between insulin and cancer has aroused huge interest but the clinical significance of this association remains uncertain and further analyses are required to clarify this issue.     

Type II diabetic subjects with secondary failure: treatment with prebreakfast mixed ultralente and regular insulin with a sulfonylurea

BACKGROUND. Combination therapy with sulfonylurea and insulin is reported to be effective in several recent reports on the management of non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea. Most of these studies used insulin twice daily, however, and hence failed to offer a significant practical advantage over insulin therapy alone. Since a subcutaneous injection of Ultralente insulin exerts its peak effect between 16 and 18 hours after injection, its prebreakfast administration is likely to inhibit overnight hepatic glucose production, which is a primary modulator of fasting plasma glucose, a major determinant of diurnal glycemia in NIDDM. Moreover, the simultaneous administration of regular insulin tends to improve glycemia during the premeal and immediate postmeal period before the onset of sulfonylurea-induced insulin secretion. METHODS. We assessed the efficacy of a prebreakfast subcutaneous injection of mixed Ultralente and regular insulin in conjunction with prior sulfonylurea therapy in 20 NIDDM subjects after precise documentation of secondary failure to these agents initially for the period of 3 months, followed by a long-term evaluation for up to 2 years. RESULTS. Metabolic control improved significantly as reflected by a decline in fasting plasma glucose (FPG) and HbA1c concentrations (FPG, 14.4 mmol/L +/- 0.4 vs 79 mmol/L +/- 0.3 mM/L; HbA1c, 11.7% +/- 0.3% vs 8.8% +/- 0.1%; P less than .001 for both comparisons). Serum cholesterol and triglycerides decreased as well, although the change was significant for triglycerides alone. Body weights and blood pressure remained unaltered. Furthermore, metabolic control appeared to remain in the same range during the long-term follow-up period. CONCLUSIONS. Adjuvant therapy with sulfonylurea and a single prebreakfast subcutaneous injection of mixed Ultralente and regular insulin may be an effective and practical therapeutic option in the management of NIDDM with secondary failure to sulfonylurea.     

The effect of combination treatment with acarbose and glibenclamide on postprandial glucose and insulin profiles: additive blood glucose lowering effect and decreased hypoglycaemia

This study compared the effects of acarbose plus glibenclamide combination therapy with acarbose or glibenclamide treatment alone on postprandial blood glucose, serum insulin and C-peptide levels, and the tendency to develop hypoglycaemia. A total of 84 patients with Type 2 diabetes (fasting blood glucose: 120-180 mg/dl; postprandial blood glucose: 140-240 mg/dl) was included in this two-centre, double-blind, double-dummy, placebo-controlled study. Patients were randomised to one of 4 treatment groups: acarbose (100 mg); glibenclamide (3.5 mg); acarbose plus glibenclamide; or placebo. Treatment was administered before a standard breakfast, and fasting (07.30 h, 08.00 h) and postprandial (09.00, 10.00, 11.00, 12.00 h) blood glucose, serum insulin and C-peptide levels were determined. Acarbose plus glibenclamide treatment significantly reduced the mean increase in postprandial blood glucose levels (23.7+/-17.3 mg/dl) compared with either acarbose (58.4+/-31.6 mg/dl), glibenclamide (56.9+/-42.8 mg/dl) or placebo (101.6+/-49.2 mg/dl) (p<0.05 for all). Serum insulin levels (mean AUC(7.30-12 h)) observed with acarbose plus glibenclamide combination therapy were significantly lower than those observed with glibenclamide monotherapy (243.5+/-161.1 vs 383.4+/-215.8 hr x microU/ml; p=0.02), and comparable with the values seen with placebo (226.0+/-166.6 hr x microU/ml), suggesting that acarbose modifies the insulin secretion induced by glibenclamide. Glibenclamide monotherapy resulted in a significantly higher rate of decrease in blood glucose level than with acarbose plus glibenclamide (71.8+/-29.9 vs 46.2+/-18.0 mg/dl x h(-1); p=0.0003), and blood glucose levels at 11.00 h were also markedly lower with glibenclamide (84.4+/-29 mg/dl) than acarbose plus glibenclamide (102.0+/-41 mg/dl), suggesting a reduced tendency for hypoglycaemic episodes with acarbose plus glibenclamide than with glibenclamide alone. In all, 6 (29%) hypoglycaemic episodes occurred with glibenclamide, 2 (10%) with acarbose plus glibenclamide and none with acarbose. Acarbose plus glibenclamide combination therapy results in an additive glucose lowering effect and reduced risk for hypoglycaemia. Acarbose modifies the insulin secretion induced by glibenclamide, which explains the lower risk of hypoglycaemia compared with glibenclamide monotherapy.     

Modification of beta-cell response to different postprandial blood glucose concentrations by prandial repaglinide and combined acarbose/repaglinide application

This study was designed to compare the effects of repaglinide plus acarbose combination treatment to repaglinide alone on postprandial glucose, serum insulin, C-peptide and proinsulin concentrations. A total of 40 patients with Type 2 diabetes (T2DM) (fasting blood glucose: 120-180 mg/dl; postprandial blood glucose: 140-240 mg/dl) were included in this single-centre, controlled, randomised, single-dose, cross-over study. On two consecutive days, patients either received 2 mg repaglinide 15 min before breakfast followed by 100 mg acarbose with breakfast or repaglinide alone. Two fasting (7.30 h, 8.00 h) and five postprandial blood samples (from 8.30 h to 12.00 h) were taken for blood glucose, serum insulin, C-peptide and proinsulin determination. Repaglinide plus acarbose treatment significantly reduced the mean increase in postprandial blood glucose levels (24.2+/-18.2 mg/dl) compared to repaglinide alone (51.1+/-29.0 mg/dl; p<0.001). Serum insulin, C-peptide and proinsulin levels [mean area under the curve (AUC7.30-12.00h)] were significantly lower than those observed with repaglinide monotherapy (e.g. insulin: 1089.2+/-604.5 hr x pmol/l and 1596.8+/-1080.6 hr x pmol/l, resp., p<0.001), suggesting that acarbose modifies the rapid insulin release induced by repaglinide. Prandial treatment with a combination of acarbose and repaglinide results in an additive glucose lowering effect and modified insulin secretion compared to repaglinide alone. Postprandial hyperglycaemia is not abolished by rapid stimulation of insulin release induced by repaglinide. Additional reduction of postprandial blood glucose by acarbose modifies the stimulation of insulin release.     

Effect of continuous subcutaneous insulin infusion vs multiple daily insulin injection with glargine as basal insulin: an open parallel long-term study

Aim of this 1-yr open parallel study was to evaluate the efficacy of two regimens of intensive insulin treatment: continuous s.c. insulin infusion (CSII) and multiple daily insulin injection (MDI) treatment with lispro plus glargine in 48 Type 1 diabetic patients that had been treated with MDI (regular or lispro insulin before each meal plus NPH) for at least 1 yr. Twenty-four patients treated with CSII, receiving lispro at multiple basal infusion rates plus boluses at meal (CSII group), were compared to 24 patients, matched for age, duration of diabetes and metabolic control, treated with MDI with lispro at each meal combined with glargine (glargine group). In the CSII group, compared to traditional MDI treatment, there was a decrease in HbA1c (9.0 +/- 1.3% during traditional MDI vs 8.0 +/- 1.0% during CSII, p<0.001), severe hypoglycaemic episodes (0.42 vs 0.17 per patient/yr, p<0.05), insulin requirement (48 +/- 11.7 vs 35.9 +/- 8.5 U/day, p<0.001). In the glargine group, compared to MDI traditional treatment, there was a decrease in HbA1c (8.6 +/- 1.1 vs 7.9 +/- 1.2%, p<0.001) and severe hypoglycaemic episodes (0.46 vs 0.21 per patient/yr, p<0.05). No significant difference between the CSII group and the glargine group was present in the degree of improvement in HbA1c and severe hypoglycaemic episodes. However, in the CSII group there was a significantly greater reduction in mean amplitude of glycaemic excursions (MAGE) and insulin requirement than in the glargine group. In conclusion, despite a similar improvement in metabolic control, CSII improves blood glucose variability when compared to MDI with glargine as basal insulin.     

Adipocyte differentiation-related protein in human skeletal muscle: relationship to insulin sensitivity

OBJECTIVE: To determine whether adipocyte differentiation-related protein (ADRP), a lipid droplet-associated protein that binds to and sequesters intracellular fatty acids, is 1) expressed in human skeletal muscle and 2) differentially regulated in human skeletal muscle obtained from obese non-diabetic (OND) and obese diabetic (OD) subjects. RESEARCH METHODS AND PROCEDURES: Ten OND subjects and 15 OD subjects underwent a weight loss or pharmacological intervention program to improve insulin sensitivity. Anthropometric data, hemoglobin A(1C), fasting glucose, lipids, and glucose disposal rate were determined at baseline and at completion of studies. Biopsies of the vastus lateralis muscle (SkM) were obtained in the fasting state from OND and OD subjects. Protein expression was determined by Western blotting. RESULTS: ADRP was highly expressed in SkM from OND (4.4 +/- 1.54 AU/10 microg, protein, n = 10) and OD (5.02 +/- 1.33 AU/10 microg, n = 12) subjects. OND subjects undergoing weight loss had decreased triglyceride levels and improved insulin action. SkM ADRP content increased with weight loss from 5.14 +/- 2.15 AU/10 microg to 9.92 +/- 1.57 AU/10 microg (p < 0.025). OD subjects were treated with either troglitazone or metformin, together with glyburide, for 3 to 4 months. Both treatments attained similar levels of glycemic control. OD subjects with lower baseline ADRP content (2.85 +/- 1.07 AU/10 microg, n = 6) displayed up-regulation of ADRP expression (to 9.27 +/- 2.76 AU/10 microg, p < 0.025). DISCUSSION: ADRP is the predominant lipid droplet-associated protein in SkM, and low ADRP expression is up-regulated in circumstances of improved glucose tolerance. Up-regulation of ADRP may act to sequester fatty acids as triglycerides in discrete lipid droplets that could protect muscle from the detrimental effects of fatty acids on insulin action and glucose tolerance.     

Lispro insulin treatment in comparison with regular human insulin in type 2 diabetic patients living in nursing homes

Lispro insulin has been demonstrated to be effective in reducing post-prandial blood glucose levels. Thirty Type 2 diabetic subjects (18 women and 12 men) living in nursing homes, aged 77 +/- 3 yr, mean systolic pressure 147 +/- 6 and diastolic 82 +/- 4 mmHg, body mass index 27.5 +/- 2 kg/m2, known diabetes duration 10.1+/- 0.7 yr, mean HbA1c 8.5 +/- 0.8%, fasting C-peptide 1.3 +/- 0.5 ng/ml, treated with intensive (4 insulin injections per day) therapy, mean insulin need 45 +/- 7 IU per day, with 2.0 +/- 0.6 hypoglycaemic (blood glucose level below 60 mg/dl) and 13 +/- 4 hyperglycaemic episodes (blood glucose level over 250 mg/dl) per wk, were studied. Their own informed consent or that provided by a family member was obtained before these patients took part in a therapy protocol divided into 3 four-mo periods; in the 1st and 3rd period regular insulin (75% of the total dose) was administered 30 min before each meal, in the second lispro insulin was administered immediately at the end of each meal, according to the carbohydrate quantity ingested with the meal. During the lispro treatment period there was a significant decrease of the mean daily blood glucose 166 +/- 12 regular vs 143 +/- 9 lispro; p<0.01, HbA1c 8.5 +/- 0.6 regular vs 7.6 +/- 0.5 % lispro; p<0.01, triglycerides 261 +/- 40 regular vs 218 +/- 20 mg/dl lispro; p<0.01, hypoglycaemic 2.1 +/- 0.2 regular vs 1.6 +/- 0.3 lispro; p<0.01 and hyperglicaemic 12 +/- 1 regular vs 8 +/- 0.3 lispro; p<0.01 episodes per wk. No statistical difference was recorded between the 1st and the 3rd treatment period. The lispro treatment produced a better metabolic control (mean blood glucose, HbA1c, triglycerides), better lifestyle (less hypo- and hyperglycaemic episodes), better nurse management (no waiting time before, but a more accurate calculation of the right dose administered immediately at the end of each meal). Lispro insulin seems to be a good therapeutic choice not only in Type 1, but also in the large population of elderly Type 2 diabetic patients.     

Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores

AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.     

Insulin resistance in nondiabetic morbidly obese patients: effect of bariatric surgery

OBJECTIVE: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. RESEARCH METHODS AND PROCEDURES: Thirteen obese patients (four men/nine women; BMI = 56.3 +/- 2.7 kg/m2) and 13 lean subjects (five men/eight women; BMI = 22.4 +/- 0.5 kg/m2) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after ( approximately 40% relative to initial body weight; Study II) weight loss induced by Roux-en-Y Gastric bypass with silastic ring surgery. RESULTS: The obese patients were insulin resistant (whole-body glucose use = 19.7 +/- 1.5 vs. 51.5 +/- 2.4 micromol/min per kilogram fat-free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 +/- 86 vs. 85 +/- 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole-body glucose use increased (35.5 +/- 3.7 micromol/min per kilogram fat-free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow-up period. Insulin-induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). DISCUSSION: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.     

沙格列汀二甲双胍缓释片联合精蛋白生物合成人胰岛素注射液（预混50R）治疗脆性糖尿病患者的临床研究

目的 探讨沙格列汀二甲双胍缓释片联合精蛋白生物合成人胰岛素注射液（预混50R）治疗脆性糖尿病的临床效果。方法 99例脆性糖尿病患者根据治疗方法的不同分为两组,对照组予以精蛋白生物合成人胰岛素注射液（预混50R）治疗,观察组在对照组基础上予以沙格列汀二甲双胍缓释片治疗,比较两组的血糖水平（FPG、 2hPG、 HbA1c）、日内血糖变异状态（SD、PPGE、 LAGE）及不良反应。结果 治疗后,两组的FPG、 2hPG、 HbA1c、 SD、 PPGE、 LAGE均显著低于治疗前,且观察组的上述指标均显著低于对照组（P <0.05）。两组的不良反应发生率比较,差异无统计学意义（P>0.05）。结论 沙格列汀二甲双胍缓释片联合精蛋白生物合成人胰岛素注射液（预混50R）治疗脆性糖尿病效果显著,可有效稳定患者的血糖水平,且安全性较高。     

Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without Type 2 diabetes

Metformin has been shown to increase glucagon-like peptide-1 (GLP-1) levels after an oral glucose load in obese non-diabetic subjects. In order to verify if this effect of the drug was also present in obese Type 2 diabetic patients who have never been treated with hypoglycemic drugs, 22 Type 2 diabetic and 12 matched non-diabetic obese patients were studied. GLP-1 was measured before and after a 100 g glucose load at baseline, after a single oral dose of 850 mg of metformin, and after 4 weeks of treatment with metformin 850 mg three times daily. Post-load GLP-1 levels were significantly lower in diabetic patients. A single dose of metformin did not modify GLP-1 levels. After 4 weeks of treatment, fasting GLP-1 increased in diabetic patients (3.8 vs 4.9 pmol/l; p<0.05), while the incremental area under the curve of GLP-1 significantly increased in both diabetic [93.6 (45.6-163.2) vs 151.2 (36.0-300.5) pmol x min/l; p<0.05] and non-diabetic [187.2 (149.4-571.8) vs 324.0 (238.2-744.0) pmol x min/l; p<0.05] subjects. In conclusion, GLP-1 levels after an oral glucose load in obese type 2 diabetic patients were increased by 4 weeks of metformin treatment in a similar fashion as in obese subjects with normal glucose tolerance.