Chronic Ethanol Feeding Impairs Glucose Tolerance But Does Not Produce Skeletal Muscle Insulin Resistance in Rat Epitrochlearis Muscle

Herein, we have investigated whether male Wistar rats develop impaired glucose tolerance after ethanol feeding. Rats were fed a liquid diet providing 35% calories from ethanol (EF) or a control diet that isocalorically replaced ethanol with maltose-dextrins for 4 weeks. Intravenous glucose tolerance was impaired in EF rats compared with pair-fed (PF), but not ad libitum (AL) controls. Areas under the intravenous glucose tolerance test curve were 5476 ± 516 mm², 3056 ± 421 mm², and 4199 ± 613 mm² ( p < 0.05) for AL, PF, and EF rats, respectively. Initial plasma insulin concentrations in EF rats were comparable with PF rats; however, 15 min after a dextrose challenge, plasma insulin levels in EF rats were 39% lower than PF rats. Because skeletal muscle is the primary sink for insulin-mediated glucose disposal, the development of skeletal muscle insulin resistance after ethanol feeding could contribute to impaired glucose tolerance. Total GLUT1 was not affected by diet in either red or white muscle. No difference in the total quantity of insulin-responsive glucose transporter, GLUT4, was observed in red muscle. In contrast, GLUT4 was 20% lower in white muscle from EF rats, compared with PF and AL rats. However, insulin-stimulated glucose transport into the epitrochlearis, a white muscle group, was not impaired with ethanol feeding. These data demonstrate that chronic ethanol feeding impairs glucose tolerance; impaired glucose tolerance was associated with an inability to maintain plasma insulin levels, rather than the development of skeletal muscle insulin resistance.     

The Acute Effect of Preprandial Exogenous and Endogenous Sulphonylurea-stimulated Insulin Secretion on Postprandial Glucose Excursions in Patients with Type 2 Diabetes

Sulphonylureas improve glucose tolerance by stimulating insulin secretion. Whether improved glucose tolerance results from enhanced early insulin release or greater total insulin secretion is not clear. Insulin responses to a test meal in Type 2 diabetic subjects with and without a single dose (2.5 mg) of oral and intravenous glipizide were, therefore, measured. Intravenous glipizide enhanced early insulin release more than oral glipizide (134% and 80% vs control; p<0.01), whereas total insulin release was equally improved (78% and 54% vs control; p<0.01). Despite slight differences in insulin release, there was no difference in glucose tolerance (median area under concentration curve (AUC); 66.6 vs 61.9 mmol × min I^?1; NS). The test meal was repeated after a bolus of intravenous insulin at the beginning of the meal. This allowed comparison of the effect of exogenous and endogenous insulin supply on postprandial glucose excursions. In spite of an early and fivefold larger rise in serum insulin after intravenous administration of the hormone than after intravenous glipizide (725% vs 134%; p<0.01), postprandial glucose was no better than after glipizide (median AUC; 87.8 vs 66.6 mmol × min I^?1; NS). In contrast, glucose tolerance was better after oral glipizide compared to intravenous insulin (median AUC; 61.9 vs 87.8 mmol × min I^?1; p<0.05). In conclusion, the total amount of insulin secreted seems more important than the timing of the insulin release for the postprandial glucose tolerance in Type 2 diabetic subjects. Neither endogenous nor peripheral pre-meal supply of insulin could normalize postprandial glucose excursions in patients with Type 2 diabetes.     

胰岛素增强低血流缺血对心肌GLUT4基因表达的刺激作用

目的　观察胰岛素是否增强低血流缺血对心肌葡萄糖转运子4(GLUT4)基因表达的刺激作用。方法　采用Northern法分析心肌GLUT4mRNA和免疫法分析心肌GLUT4多肽。比较单纯给予胰岛素、单纯心肌缺血和心肌缺血时给予胰岛素心肌GLUT4mRNA和GLUT4多肽的表达情况,并与正常心肌比较。结果　正常心肌GLUT4mRNA和GLUT4多肽心外层分别为1.3±0.16;0.72±0.01(relativedens,units),心内层分别为1.4±0.15;0.73±0.01。单纯给予胰岛素心肌GLUT4mRNA表达比正常心肌增加1.2倍,GLUT4多肽表达增加1倍(P<0.05);单纯缺血心肌则分别增高1.7和1.8倍(P<0.01);而心肌缺血时给予胰岛素GLUT4mRNA表达增高2.5倍,GLUT4多肽表达则增加2.3倍(P<0.01)。心肌葡萄糖摄取量亦比正常心肌明显增高。结论　胰岛素与低血流缺血均能刺激心肌GLUT4mRNA和GLUT4多肽表达,而心肌缺血时给予胰岛素则增强缺血刺激的GLUT4mRNA和GLUT4的表达作用,其结果使GLUT4数明显增加,进而使心肌葡萄糖摄取量相应增加。胰岛素增强低血流缺血对心肌GLUT4表达的刺激作用,在缺血心肌能量代谢过程中起着重要的代偿性平衡作用。     

神经肌肉电刺激对糖尿病大鼠GLUT4基因表达的影响

目的研究神经肌肉电刺激（neuromuscular electrical stimulation, NMES）对糖尿病大鼠股四头肌葡萄糖轻运载体4（glucose transporter 4, GLUT4）表达的影响。 方法选取24只2型糖尿病大鼠,数字表法随机分为空白组、运动组、NMES组,每组各8只。运动组给予中等强度跑台训练干预;NMES组对大鼠双下肢股四头肌进行NMES。通过尾静脉采血测空腹血糖水平,采用酶联免疫吸附分析法检测大鼠胰岛素水平并计算胰岛素抵抗指数（insulin resistant index, IRI）,采用RT-PCR法测定股四头肌GLUT4基因表达量。多组间的比较采用方差分析,进一步两组间的比较采用LSD-t检验。 结果运动组和NMES组实验干预后血糖水平均显著下降（均P<0.01）,空白组干预前后血糖水平无明显变化（均P>0.05）。3组大鼠实验干预前后胰岛素水平均无明显改变（t=1.023、2.283、1.775,均P>0.05）;实验干预后运动组和NMES组IRI较实验干预前明显改善（t=10.216、6.748,均P<0.01）。实验干预前,3组大鼠空腹血糖水平及IRI无明显差异（F=1.138、1.040,均P>0.05）;实验干预后,3组大鼠空腹血糖水平、IRI及GLUT4 mRNA表达水平的差异有统计学意义（F=38.415、9.976、275.123,均P<0.01）。实验干预后,运动组和NMES组血糖水平及IRI均显著低于空白组（均P<0.01）,股四头肌GLUT4 mRNA的表达水平均显著高于空白组（均P<0.01）;运动组与NMES组血糖水平及IRI的差异均无统计学意义（均P>0.05）,运动组大鼠股四头肌GLUT4 mRNA的表达水平显著高于NMES组（P<0.01）。 结论NMES训练可以降低糖尿病大鼠空腹血糖、改善胰岛素抵抗,其作用机制可能与骨骼肌GLUT4基因mRNA水平上调有关。     

胰岛素+达格列净治疗2型糖尿病的效果和对患者血糖的影响探讨

目的 探讨胰岛素+达格列净治疗2型糖尿病的效果和对患者血糖的影响.方法 将该院2018年10月—2020年6月期间治疗2型糖尿病患者88例作为研究对象,所有患者均采用常规降糖药物胰岛素进行治疗,根据是否联合应用达格列净药物分为两组,每组44例,对照组给予常规降糖药物进行治疗,试验组则在对照组基础上联合应用达格列净片,所...     

2型糖尿病运用早期胰岛素强化治疗的疗效及对患者血糖水平的影响分析

目的 探究早期胰岛素强化治疗方案在2型糖尿病(T2DM)患者中的应用价值.方法 选取2018年4月—2020年4月收治的108例T2DM患者进行回顾性分析,依据治疗方案的不同分为对照组(n=54)与观察组(n=54),对照组均采用阶梯式治疗,观察组则实施早期胰岛素强化治疗,对比两组患者治疗前后的血糖水平、胰岛功能、脂质...     

Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes

Aims/hypothesis Exercise enhances insulin-stimulated glucose transport in skeletal muscle through changes in signal transduction and gene expression. The aim of this study was to assess the impact of acute and short-term exercise training on whole-body insulin-mediated glucose disposal and signal transduction along the canonical insulin signalling cascade.Methods A euglycaemic–hyperinsulinaemic clamp, with vastus lateralis skeletal muscle biopsies, was performed at baseline and 16 h after an acute bout of exercise and short-term exercise training (7 days) in obese non-diabetic (n=7) and obese type 2 diabetic (n=8) subjects.Results Insulin-mediated glucose disposal was unchanged following acute exercise in both groups. Short-term exercise training increased insulin-mediated glucose disposal in obese type 2 diabetic (p<0.05), but not in obese non-diabetic subjects. Insulin activation of (1) IRS1, (2) IRS2, (3) phosphotyrosine-associated phosphatidylinositol-3 kinase activity and (4) the substrate of phosphorylated Akt, AS160, a functional Rab GTPase activating protein important for GLUT4 (now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) translocation, was unchanged after acute or chronic exercise in either group. GLUT4 protein content was increased in obese type 2 diabetic subjects (p<0.05), but not in obese non-diabetic subjects following chronic exercise.Conclusions/interpretation Exercise training increased whole-body insulin-mediated glucose disposal in obese type 2 diabetic patients. These changes were independent of functional alterations in the insulin-signalling cascade and related to increased GLUT4 protein content.     

Changes in Glucose Disposal and Cellular Insulin Binding in Obese Black Southern African Patients with Type 2 Diabetes Mellitus Before and After Sulphonylurea Therapy

Peripheral insulin action and cellular insulin binding were studied in 10 newly detected, obese, black, Southern African women with Type 2 diabetes mellitus before and after midterm oral sulphonylurea therapy and in five obese, non-diabetic controls. Glucose disposal (assessed by the euglycaemic insulin clamp technique) was significantly reduced in diabetic patients compared to control subjects (4.4 ± 0.5 vs 6.4 ± 0.5 mg kg^-1 min^-1, p < 0.05), and increased after 1 and 3 months of sulphonylurea therapy to 6.8 ± 0.6 mg kg^-1 min^-1 (p = 0.01) and 6.3 ± 0.7 mg kg^-1 min^-1 (p = 0.04), respectively. The major change in the binding kinetics of insulin to peripheral monocytes was an increase in the mean receptor concentration in the diabetic patients which was significant after 3 months of therapy (0.2 ± 0.08 to 0.6 ± 0.01 nM, p = 0.05). The basal plasma C-peptide concentration was significantly lower in the diabetic patients than in the controls and remained so following sulphonylurea therapy, despite significant reductions in fasting glucose and HbA_-1 concentrations. We conclude that newly diagnosed, obese, black Southern Africans with Type 2 diabetes showed diminished peripheral glucose disposal which increased following sulphonylurea therapy. This was accompanied by an increase in insulin receptor concentration but not with changes in basal insulin secretion.     

The Effect of Acarbose on Blood Glucose Profiles of Type 2 Diabetic Patients Receiving Insulin Therapy

Nine patients with Type 2 diabetes receiving insulin therapy were treated with acarbose 100 mg thrice daily for 1 week to investigate the effect of acarbose on blood glucose control. Daily blood glucose profiles contained fewer excursions during acarbose administration and low levels were maintained. The M-value, an indicator of blood glucose fluctuation, decreased significantly from a run-in period value of 37.6 ± 8.7 (SEM) to 16.7 ± 4.0 during the acarbose period (p < 0.05) and rose again to 28.9 ± 6.7 (p ≧ 0.05) in the follow-up period. The 24-h urinary glucose excretion similarly decreased during acarbose administration. As expected, no decrease in HbA_1c was observed due to the short treatment period. The 24-h urinary C-peptide excretions and serum lipids were not influenced by acarbose therapy. Frequent episodes of clinical hypoglycaemia were experienced while on acarbose therapy, indicating a decrease in insulin requirements. Adverse events such as flatulence and abdominal distention were observed in six out of nine cases. Symptoms were generally mild and well tolerated, only one patient dropped out because of diarrhoea and abdominal pain. We conclude that acarbose could usefully be administered to Type 2 diabetic patients treated with insulin to improve blood glucose control and reduce insulin requirement if the appropriate selection criteria were met.     

More Uniform Diurnal Blood Glucose Control and a Reduction in Daily Insulin Dosage on Addition of Glibenclamide to Insulin in Type 1 Diabetes Mellitus: Role of Enhanced Insulin Sensitivity

Combination therapy with insulin and sulphonylurea has gained acceptance in management of subjects with Type 2 (non-insulin-dependent) diabetes mellitus. However, its role in management of Type 1 (insulin-dependent) diabetes mellitus remains controversial. In this study, the effect of combination therapy with insulin and glibenclamide on metabolic control, daily insulin dosage, and insulin sensitivity was assessed in subjects with Type 1 diabetes mellitus. Ten men with Type 1 diabetes mellitus participated in a randomized, double-blind, crossover, clinical trial with three treatment regimens, namely (1) insulin alone, (2) insulin and placebo, (3) insulin and glibenclamide, each lasting 3 months. Combination therapy induced: (1) reduction in daily insulin dosage; (2) more uniform blood glucose control as reflected by a lower average 24 h blood glucose level, a smaller difference between mean preprandial and 2 h postprandial blood glucose concentrations, decreased 24 h urine glucose excretion, and a decline in number of hypoglycaemic events; (3) improved insulin sensitivity as expressed by more rapid plasma glucose disappearance rate, without a significant alteration in fasting plasma glucagon and 1 h postprandial serum C-peptide levels; when compared with treatment with either insulin alone or with insulin and placebo. Therefore, it is apparent that the addition of glibenclamide to insulin reduces daily insulin dosage and renders a greater uniformity to diurnal blood glucose control, most probably secondary to enhancement of insulin sensitivity.     

Feasibility and Efficacy of Intensive Insulin Therapy in Type 1 Diabetes Mellitus in Primary Care

To determine the feasibility and efficacy of structured education in intensive insulin therapy (IIT) in patients with Type 1 diabetes mellitus commonly attended by primary care physicians, a prospective case-control study was carried out in co-operation with 26 general practitioners in rural Alpine region and the diabetes service at the University of Vienna, Medical School, Austria. From 89 rural Type 1 diabetic patients on conventional insulin therapy (CIT), those volunteering for better diabetes care (n = 52) were trained in IIT in the diabetes education centre and subsequently received their outpatient service by their general practitioners, as did those remaining on CIT (n = 37). Patients were matched as case-controls (n = 36 in each therapy group) for metabolic control at baseline (IIT/CIT: HbA_1c 8.2 ± 1.8 vs 8.1 ± 2.0%, ns), age, duration of diabetes, incidence of retinopathy and nephropathy. Analysing an observation period of > 4.5 years, patients trained in IIT presented with improved metabolic control as compared to those on CIT (Mean HbA_1c: IIT, 6.9 ± 1.0%; CIT, 7.9 ± 1.3%, p < 0.05, ANOVA). No difference between groups was, however, observed at the end-point of the study in HbA_1c (IIT, 7.3 ± 1.3%; CIT, 7.8 ± 1.4%; IIT vs CIT, p = 0.14) and in the development of diabetic microangiopathy, frequency of reported severe hypoglycaemic episodes, and increase in body weight. Structured in-hospital education of self-selected Type 1 diabetic patients in intensive insulin therapy permits improvement of metabolic control in the setting of a rural general practice without striking drawbacks compared to conventional insulin therapy over a period of > 4.5 years. The deterioration in metabolic control at the end-point of the study suggests the need for periodic reinforcement of transferred knowledge to continuously maintain better diabetes care.     

Insulin Loss at the Injection Site in Children with Type 1 Diabetes Mellitus

A simple filter paper technique is described for demonstrating and measuring insulin loss at the injection site in children with type 1 diabetes mellitus. Using this technique in a cohort of 19 children during a 7-day period, measurable fluid was demonstrated at the injection site in 68% of children at least once and was present following 23% of all injections. In nearly 80% of cases the insulin loss probably represented less than 1 unit but could on occasions be 2 units or more or up to 18% of the injected dose. Insulin losses were observed following injections given by children themselves and by parents. There was no significant relationship between insulin dose and insulin loss. Insulin losses at the injection site are frequent and, although usually small in amount, are a potential source of blood glucose variability.     

Glucose Profiles in Children Two Years After the Onset of Type 1 Diabetes

The relationship of 24-h glucose profiles to age, haemoglobin A_1c (HbA_1c), and C-peptide concentration was analysed in consecutive, unselected children who had developed Type 1 diabetes 2 years earlier. Seventy-seven children in four age groups (age 2–4 years, n = 9; 5–8 years, n = 14; 9–12 years, n = 26; and 13–17 years, n = 28) were studied. Each child was hospitalized for 2 days for the investigations. Mean blood glucose concentration was 9.7 ± 4.1 (SD) mmol l^?1 in children aged 2–4 years; 10.7 ± 4.0 mmol l^?1 in those aged 5–8 years; 11.3 ± 3.4 mmol l^?1 in those aged 9–12 years; and 9.8 ± 3.3 mmol l^?1 in those aged 13–17 years. Results were > 7.0 mmol l^?1 in 69% (range 56–76%) and > 10 mmol l^?1 in 49% (39–57%) of the measurements. Values decreased by 30% (21–43%) between 10 pm and 3 am. The nadir of the mean profiles of the groups was always at 3 am. Glucose concentration was < 3.0 mmol l^?1 in 25% (14–50%), < 2.5 mmol l^?1 in 9.6% (0–21%), and < 2.0 mmol l^?1 in 2.7% (0–4.2%) of the children at 3 am; hypoglycaemia was most common in those aged 5–8 years. Of the four profile characteristics used, mean blood glucose predicted HbA_1c (R² = 24.7%, p < 0.00005, multiple linear regression analysis), and slightly more in combination with age (R² = 32.0%, p < 0.00005). The means, AUCs and coefficients of variation of the glucose profiles were not different in C-peptide positive and C-peptide negative children of the age groups (p = NS, two-way ANOVA). We conclude that glucose profiles frequently uncover otherwise poorly recognizable disturbances of metabolic contol in children with diabetes.     

Type 2 (non-insulin-dependent) diabetes mellitus and glucose transporter gene (GLUT 1 andGLUT 4) polymorphism

Glucose transporter genes have been proposed as candidate genes for type 2 (non-insulin-dependent) diabetes mellitus. We chose to study the adult skeletal muscle glucose transporter gene (GLUT 4) andGLUT 1 in consideration of previous conflicting results obtained by different authors. We studied 68 patients with type 2 diabetes, and 66 non-diabetic controls matched for age, sex, and body mass index (BMI). Women and men were considered separately, according to BMI (24.0 and >24.0 for women; 25.0 and >25.0 for men). Allele and genotype frequencies were not significantly different in controls and in type 2 diabetic patients. ForGLUT 1 allele 1 and genotype x1x1 were more frequent, although not significantly (P=0.064 at ²,P=0.025 at Fisher exact test) in overweight/obese diabetic women than in overweight/obese non-diabetic women. These data do not support the hypothesis that these genes play a major role in genetic susceptibility to type 2 diabetes mellitus, but suggest a possible association, at least in women, of allele 1 ofGLUT 1 with obese type 2 diabetes mellitus.     

The Relationship Between Plasminogen Activator Inhibitor-1 and Insulin Resistance in Newly Diagnosed Type 2 Diabetes Mellitus

It is not clear whether elevated levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1) in Type 2 diabetes mellitus are the result of obesity or coexistent atherosclerosis. Therefore the relationship between PAI-1 and insulin resistance, determined by the homeostasis model assessment (HOMA) was investigated in a group of 26 insulin-resistant, normotensive newly diagnosed Type 2 diabetic patients with a low probability of atherosclerosis. Compared with a normal control group, closely matched for body mass index (BMI), fibrinolytic activity was depressed in the diabetic patients due to elevated levels of the inhibitor PAI-1, 17.6 (11.1–28) vs 8.4 (4.9–14.1) IU ml^?1, p < 0.001. PAI-1 was related to BMI, r = 0.59, p < 0.001 plasma insulin, r=0.66, p < 0.001; insulin resistance, r = 0.54, p< 0.005 and urinary albumin excretion, r=0.48, p < 0.01, but not HbA_1c or fasting glucose. PAI-1 was not related to blood pressure or plasma triglyceride levels. This study suggests that at the time of diagnosis of Type 2 diabetes mellitus, elevated PAI-1 levels are already linked to other risk factors for vascular disease including hyperinsulinaemia, insulin resistance, and urinary albumin excretion, and this is not the result of obesity or coexistent atherosclerosis.     

黄芪多糖对2型糖尿病大鼠GLUT4mRNA表达的影响

目的 探讨黄芪多糖对2型糖尿病(T2DM)大鼠脂肪组织葡萄糖转运蛋白4(GLUT4)基因表达的影响.方法 将Wistar大鼠随机分为正常对照组、模型组、黄芪多糖高、中、低剂量治疗组.用药12w后,RT-PCR检测GLUT4 mRNA基因表达水平.结果 黄芪多糖高、中剂量治疗组GLUT4 mRNA表达高于模型组.结论 黄芪多糖可上调T2DM大鼠GLUT4 mRNA表达,从而实现其降血糖作用.     

Insulin Therapy Increases Low Plasma Growth Hormone Binding Protein in Children with New-onset Type 1 Diabetes

This study was undertaken (1) to evaluate growth hormone binding protein (GHBP) levels in newly diagnosed patients with Type 1 diabetes before and after insulin therapy and (2) to determine the relationship of GHBP to glycaemic control, C-peptide level and blood pH. GHBP, expressed as a percentage of (¹²⁵I)GH bound, was determined in 33 patients with Type 1 diabetes (M/F = 19/14, 12.3 ± 0.4 years) before (day 0), after 5 days (day 5) and after 3 months (month 3) of insulin therapy. At day 0, GHBP was lower in Type 1 diabetes compared with 38 matched healthy control subjects (3.9 ± 0.4 vs 8.2 ± 0.4 %, p < 0.001). There was no significant improvement in GHBP at day 5 (4.4 ± 0.3 %). At month 3, GHBP increased to (6.0 ± 0.4 %, p < 0.001 vs day 0), but was still lower than controls, p < 0.001. At day 0 GHBP correlated with BMI (r = 0.50, p = 0.001), blood glucose (r = ?0.43 p = 0.006) and pH (r = 0.48, p = 0.004), but not HbA₁. GHBP at month 3 correlated with day 0 C-peptide (r = 0.41, p = 0.02). Thus, (1) circulating GHBP is low in newly diagnosed patients with Type 1 diabetes, and increases after 3 months of insulin therapy but does not normalize and (2) the severity of biochemical derangement and residual β-cell function at diagnosis may determine GHBP status and its recovery. We conclude that insulin is an important modulator of GH binding protein in newly diagnosed children with Type 1 diabetes.     

Effects of glipizide on glucose metabolism and muscle content of the insulin-regulatable glucose transporter (GLUT 4) and glycogen synthase activity during hyperglycaemia in type 2 diabetic patients

To examine whether sulphonylureas influence hyperglycaemia-induced glucose disposal and suppression of hepatic glucose production (HGP) in type 2 diabetes mellitus, a 150-min hyperglycaemic (plasma glucose 14 mmol/l) clamp with concomitant somatostatin infusion was used in eight type 2 diabetic patients before and after 6 weeks of glipizide (GZ) therapy. During the clamp a small replacement dose of insulin was given (0.15 mU/kg per min). Isotopically determined glucose-induced glucose uptake was similar before and after GZ administration which led to improved glycaemic control (basal plasma glucose 12.2±1.3 vs 8.9±0.7 mmol/l;P<0.01). Glucose-induced suppression of HGP was, however, more pronounced during GZ treatment (0.96±0.14 vs 1.44±0.20 mg/kg per min;P<0.02). Following GZ treatment hyperglycaemia failed to stimulate glycogen synthase activity. Moreover, GZ resulted in a significant increase in the immunoreactive abundance of the insulin-regulatable glucose transport protein (GLUT 4) (P<0.02). In conclusion, these results suggest that GZ therapy in type 2 diabetic patients enhances hepatic sensitivity to hyperglycaemia, while glucose-induced glucose uptake remains unaffected. In addition, GZ tends to normalize the activity of glycogen synthase and increases the content of GLUT 4 protein in skeletal muscle.     

Improved Blood Glucose Control by Insulin Therapy in Type 2 Diabetic Patients Has No Effect on Lipoprotein(a) Levels

The effects of improved blood glucose control by insulin therapy on lipoprotein(a) and other lipoproteins were studied in 54 patients with Type 2 diabetes (mean ± SD: age 67 ± 9 years, body mass index 26.1 ± 4.4 kg m^?2, median duration of diabetes 10 (range 1–37) years, 23 males, 31 females), who were poorly controlled despite diet and maximal doses of oral hypoglycaemic agents. After 6 months of insulin treatment, mean fasting blood glucose concentrations had decreased from 14.1 ± 2.2 mmol l^?1 to 8.4 ± 1.8 mmol l^?1 (p < 0.001), and HbA^1c had fallen from 11.1 ± 1.4 % to 8.2 ± 1.1 % (p < 0.001). Significant decreases of total and LDL cholesterol, triglycerides, apolipoprotein B, and free fatty acids were observed, while HDL-cholesterol and apoA1 increased by 10 %. Baseline serum Lp(a) levels were elevated compared to non-diabetic subjects of similar age (median 283, range 8–3050 mg I^?1, vs 101, range 8–1747 mg I^?1, p < 0.05), but did not change with insulin, and there was no correlation with the degree of metabolic improvement and changes in Lp(a) levels. It is concluded that improved blood glucose control by insulin therapy does not alter elevated Lp(a) levels in Type 2 diabetic patients, but has favourable effects on the other lipoproteins.