Effect of Aprotinin on Insulin Sensitivity in Non-insulin-dependent Diabetes Mellitus

It has been suggested that kallikrein-kinin system may influence carbohydrate metabolism via a kinin-mediated increment of insulin-mediated glucose uptake. To evaluate the effect of acute inhibition of the kallikrein-kinin system on insulin sensitivity, a randomized, placebo-controlled, double-blind study was performed in 15 male non-insulin-dependent diabetic patients. After basal evaluation of insulin sensitivity with a 2-h euglycaemic hyperinsulinaemic clamp (40 mU m⁻² min⁻¹), patients were infused either with aprotinin (200 000 U.I.C. as intravenous bolus injection) or placebo (10 ml isotonic saline) in a cross-over fashion, at 1 week intervals. After both saline and aprotinin infusions, insulin sensitivity was reassessed by continuing the euglycaemic hyperinsulinaemic clamp for a further 1 h. Resulting data showed that aprotinin significantly improved total glucose uptake (from 16.2 ± 2.9 μmol kg min⁻¹ to 20.6 ± 4.9 μmol kg min⁻¹, p<0.01), and decreased metabolic clearance rate of insulin (from 586 ± 57 ml m⁻² min⁻¹ to 442 ± 155 ml m⁻² min⁻¹, p<0.05). Thus, in spite of the suggested positive effects of kinins on insulin-mediated glucose uptake, acute inhibition of the kallikrein-kinin system resulted in a paradoxical increment of insulin sensitivity, which was probably mediated by the reduced metabolic clearance rate of insulin.     

Recurrent Hypoglycaemia Associated with First and Second Trimester Insulin Sensitivity in a Patient with Insulin-dependent Diabetes

A 35-year-old insulin-dependent diabetic woman presented at 8 weeks gestation with multiple severe hypoglycaemic episodes occurring during the day and night without warning. Her pre-pregnancy insulin dosage of 45 units daily was progressively reduced by 73 % to 12 units daily by week 17 because of multiple hypoglycaemic episodes. Investigation showed no pathological cause for the hypoglycaemia. Insulin dosage increased to 16 units daily by week 19 and then increased sharply to 60 units daily at 23 weeks and finally to 72 units at week 37. Following delivery her insulin dosage returned to pre-pregnancy values. Insulin-dependent diabetic women may rarely develop exaggerated insulin sensitivity in the first trimester of pregnancy resulting in severe hypoglycaemia, but spontaneous improvement occurs with increasing insulin resistance in the second and third trimesters.     

Body Adiposity Index and Body Roundness Index in Identifying Insulin Resistance Among Adults Without Diabetes

Background

Body adiposity index (BAI) and body roundness index (BRI), initially developed to assess obesity, were evaluated here to detect insulin resistance in comparison with traditional anthropometric indices of body mass index (BMI), waist circumference (WC), weight-to-height ratio (WHtR), visceral adiposity index (VAI) and abdominal volume index (AVI).

Obese Patients with Type 2 Diabetes Poorly Controlled by Insulin and Metformin: Effects of Adjunctive Dexfenfluramine Therapy on Glycaemic Control

Dexfenfluramine is well known for its weight reducing action and has been reported to improve glycaemic control in obese Type 2 diabetic patients not adequately controlled on conventional oral hypoglycaemic therapy. In this double-blind placebo-controlled study, 20 obese Type 2 diabetic patients with mean HbA_1c of 8.8 ± 0.5% (normal range 3.5–6.0%), and mean body mass index (BMI) of 34.4 ± 1.0 kg m^?2, who were poorly controlled on insulin (mean dosage 58.0 ± 6.1 units day^?1) were randomized to receive either additional dexfenfluramine or placebo for 12 weeks. Seventeen of these patients were already taking maximum tolerated metformin therapy (mean dosage 1.6 ± 0.2 g day^?1) and the other three were unable to tolerate any at all. At baseline, the dexfenfluramine and placebo groups were similar in all parameters studied. After the 12-week treatment period, median HbA_1c had fallen in dexfenfluramine treated patients from 8.5 (interquartile range (IR): 7.5–10.3) to 7.1% (IR: 6.7–7.5; p < 0.02). The fall in HbA_1c in individual patients after treatment with dexfenfluramine was strongly associated with weight loss (r = 0.69; p < 0.04), although as a group the changes in weight and BMI were not statistically significant. Placebo was without effect. These results show that in the obese patient with Type 2 diabetes who is poorly controlled despite large daily doses of insulin and metformin, adjunctive dexfenfluramine can improve glycaemic control without exacerbating weight gain.     

Albuminuria,Insulin Resistance and Dyslipidaemia in Chinese Patients with Non-insulin-dependent Diabetes (NIDDM)

In order to examine the relationships between albuminuria, insulin resistance, and dyslipidaemia in non-insulin-dependent diabetes (NIDDM), we studied 164 Chinese patients (68 men, 96 women), treated with diet or oral hypoglycaemic agents, on three occasions during a 6-week period. Antihypertensive treatment, if previously prescribed, was withdrawn for at least 2 weeks before the study period. Insulin resistance was calculated from simultaneous fasting plasma glucose and insulin concentrations using the homeostasis model assessment (HOMA) method. Based on two of three 24 h urinary collections, 87 (53 %) patients had normoalbuminuria, 46 (28 %) microalbuminuria, and 31 (19 %) macroalbuminuria. Despite similar glycaemic control, patients with abnormal albuminuria had higher mean arterial pressure, fasting plasma total cholesterol, triglyceride and serum apo B concentrations and were more insulin resistant than normoalbuminuric patients. Albuminuria correlated with mean arterial pressure (r = 0.31, p < 0.001), triglyceride (r = 0.36, p<0.001), total cholesterol (r = 0.28, p = 0.001), apolipoprotein B (apo B) (r = 0.25, p = 0.003), and insulin resistance (r = 0.25, p < 0.002). These close associations may contribute to the increased cardiovascular risk in Chinese NIDDM patients with abnormal albuminuria.     

Beta-cell Dysfunction in First-degree Relatives of Patients with Non-insulin-dependent Diabetes Mellitus

To analyse the relationship between age, glucose tolerance, beta-cell function, and insulin sensitivity in preclinical states of non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), we have done a cross-sectional, age-stratified analysis of 86 non-diabetic first-degree relatives of NIDDM patients and 49 controls with similar age, sex, and BMI. A 5 mg kg ideal body weight⁻¹ min⁻¹ for 60 min of continuous infusion of glucose with model assessment (CIGMA) of serum glucose and C-peptide values at the end of the infusion was used to determine glucose tolerance and beta-cell function. Insulin sensitivity was estimated by modelling basal serum glucose and insulin values. Relatives and controls were divided into tertiles on the basis of age. Relatives had higher basal (5.3 vs 5 mmol l⁻¹, p = 0.02) and achieved serum glucose (9.1 vs 8.4 mmol l⁻¹, p = 0.01), lower beta-cell function (128 vs 145 %, p = 0.007), and lower insulin sensitivity (37 vs 43 %, p = 0.002). Beta-cell function declined with age in relatives (from 139 % in young subjects to 134 % in intermediate subjects and to 111 % in older subjects, p = 0.002) and this decline was associated with an increase in basal serum glucose (from 5.1 to 5.3 and to 5.7 mmol l⁻¹, p = 0.000) and achieved glucose (from 8.3 to 9.1 and to 9.3 mmol l⁻¹, p = 0.038), without significant changes in insulin sensitivity. These trends were observed even after the exclusion of subjects with mild glucose intolerance. We conclude that both beta-cell dysfunction and insulin resistance are present in first-degree relatives of NIDDM. The progression of beta-cell dysfunction and glucose intolerance with age suggests that beta-cell dysfunction is the key factor in the apparition and progression of the disease.     

Lipid Composition of Platelets in Patients with Non-insulin-dependent Diabetes Mellitus: Studies Before and After Treatment of Diabetes

The study was designed to investigate whether impaired composition of platelet lipids in untreated diabetic patients improved after diabetic treatment. Fourteen untreated patients with non-insulin-dependent diabetes mellitus (NIDDM) and 15 healthy control subjects were studied. In the diabetic patients, the ratio of free cholesterol to phospholipid (FC/PL) in platelets of 0.33 ± 0.02 (mean ± SEM) at pre-treatment, which was statistically (p < 0.05) higher than that of 0.26 ± 0.02 in control subjects, was significantly decreased to the value of 0.29 ± 0.02 (p < 0.01) after insulin therapy. Platelet FC level of 9.77 ± 0.77 μg 10^?8 cells pre-treatment was significantly (p < 0.01) reduced to the value of 7.72 ± 0.38 μg 10^?8 cells post-treatment. Platelet PL level showed no significant changes after the treatment. There was a significantly (p < 0.01) positive correlation between the decrease in FC/PL of platelets and that in haemoglobin A_1c (HbA_1c) after treatment for diabetes (rs = ?0.729). These results indicate that the impaired lipid composition in platelets can be improved after an adequate glycaemic control in patients with NIDDM.     

Body Composition and Inflammation in Hemodialysis Patients

The volume state of dialysis patients is important in guiding the dialysis process. Volume overload in these patients is associated with inflammation. The objectives of the present study were to assess the body composition of patients on hemodialysis; to determine the concentrations of B‐type natriuretic peptide (BNP) in plasma and evaluate the association of BNP concentrations with volume overload; to determine the concentrations of C‐reactive protein (CRP), albumin and superoxide dismutase (SOD) activities as indicators of inflammatory or antioxidant processes. The study included 79 maintenance hemodialysis patients. Assessment of body compartments was carried out using a body composition monitor (BCM). After BCM measurements, blood samples were taken from the patients for laboratory tests. There were 40 (50.6%) volume‐overloaded patients (relative overhydration >15%). These patients had a higher prevalence of arterial hypertension (P < 0.05), significantly higher concentrations of BNP (P = 0.01), lower body mass index (P < 0.05) and lower fat tissue index (P < 0.05). There was a positive correlation between plasma BNP and CRP concentrations (ρ = 0.231; P < 0.05), and a negative correlation between (log) BNP and albumin (r = ?0.021; P < 0.05), as well as (log) CRP and albumin concentrations (r = ?3; P < 0.01). SOD activity was positively correlated with albumin concentrations (r = 0.254; P < 0.05). The concentrations of BNP in this study were associated with volume overload and inflammatory markers. Patients with a higher albumin concentration had higher SOD activity.     

老年糖尿病患者合并感染后胰岛素泵强化治疗的有效性分析

目的研究老年糖尿病患者合并感染后胰岛素泵强化治疗的有效性。方法该次纳入2018年5月-2019年4月收治的104例老年糖尿病合并感染患者展开研究,按照随机数字表法分为两组,对照组52例予以胰岛素皮下注射治疗,观察组52例实施胰岛素泵强化治疗。将两组的血糖指标、治疗相关情况进行比对。结果观察组老年糖尿病合并感染患者治疗后的空腹血糖、餐后2 h血糖均低于对照组,血糖达标时间、感染控制时间、住院时间短于对照组,胰岛素日用量少于对照组(P<0.05)。结论胰岛素泵强化治疗老年糖尿病合并感染患者的血糖控制及感染控制效果显著。     

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.     

Importance of Early Insulin Levels on Prandial Glycaemic Responses and Thermogenesis in Non-insulin-dependent Diabetes Mellitus

To examine the effect of different profiles of insulin administration on glycaemia and thermogenesis, we studied 10 subjects with mild non-insulin-dependent diabetes mellitus on four occasions after a standard mixed meal: (1) with no supplementary insulin (control), (2) with intravenous insulin (1.8***U over 15 min = short), (3) as for short but extended over 30 min to simulate the normal initial rise in portal vein insulin levels (medium), (4) as for medium with additional insulin to normalize the profile from 30–60 min (3.6***U over 60 min, long). All studies in which supplemental insulin was administered lowered the integrated glucose response above baseline versus the control study (short 76%, medium 71%, and long 56% of control, p = 0.003). The insulin infusions also increased the non-protein respiratory quotient in the first hour following the meal (0.82 ± 0.01 (control) vs 0.87 ± 0.01 (short), 0.86 ± 0.01 (medium) and 0.87 ± 0.01 (long), p = 0.003) and augmented thermogenesis (7.6 ± 1.5 (control) vs 10.5 ± 2.9 (short), 13.0 ± 1.9 (medium) and 13.2 ± 2.8% (long), p = 0.02). Total integrated insulin area above baseline was significantly greater in the long study (short 121, medium 111 vs long 179% of control, p = 0.02). Thus the greatest glycaemic benefit in relation to insulinaemia was obtained with the two shorter insulin infusions (short and medium). In conclusion, this study confirms the role of early prandial insulin secretion (or delivery) in limiting prandial glycaemia in NIDDM and increasing thermogenesis and highlights the pivotal role of the timing of elevation of insulin levels in modulating hyperglycaemia and hyperinsulinaemia.     

Human Insulin Receptor Substrate-1: Variant Sequences in Familial Non-insulin-dependent Diabetes Mellitus

The aetiology of NIDDM is uncertain, although family and twin studies indicate an important role for genetic factors in disease onset. The function and position of IRS-1 within the insulin signalling pathway make it a prime candidate gene for the development of insulin resistance and NIDDM. Insulin resistant families were identified by studying unaffected first degree relatives from families with 2 or more living NIDDM subjects. Insulin sensitivity was determined in the relatives using the insulin tolerance test, and 15 families were identified as insulin resistant. One NIDDM subject from the 10 most resistant families was selected and the entire coding region of IRS-1 analysed by SSCP analysis. Four normoglycaemic subjects with no family history of diabetes served as controls. Five variant sequences of IRS-1 were identified within the NIDDM subjects; 2 silent polymorphisms at codons 235 (GGG to GGA) and 893 (CCG to CCC): 2 non-conservative mutations (Ala₅₁₃Pro; Gly₉₇₂Arg) and a codon deletion (Ser_681-7 to Ser_681-6). The influence of the non-conservative mutations alone, and in combination with other abnormalities of the insulin signalling pathway on peripheral insulin action, remains to be determined.     

Alcohol Ingestion and Glycaemic Control in Patients with Insulin-dependent Diabetes Mellitus

It is widely accepted that alcohol consumption by patients with insulin-dependent (Type 1) diabetes mellitus is associated with an increased risk of hypoglycaemia. This association has been the subject of few studies, however, and there is not much evidence to support advice currently given to patients. Available information suggests that moderate alcohol consumption by healthy, fed subjects does not cause acute hyper- or hypoglycaemia although there may be a delayed risk of hypoglycaemia the morning after evening alcohol intake. Alcohol can lead to potentially hazardous hypoglycaemia in fasted individuals or in those dependent upon alcohol and has been associated with hypoglycaemic unawareness. © 1997 by John Wiley & Sons, Ltd.     

Physical Activity, Body Mass Index, and Diabetes Risk in Men: A Prospective Study

Objective

Physical activity has been associated with lower diabetes risk, but several prospective studies among women found that activity only slightly attenuated the diabetes risk associated with high body mass index (BMI). We investigated the independent and joint associations between vigorous activity and BMI on diabetes risk in men.

Methods

This was a prospective cohort design within the Physicians' Health Study, using Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident diabetes in 20,757 men without diabetes at baseline. Models were based on self-reported BMI and exercise frequency at baseline, first separately and then with a 6-category joint variable combining World Health Organization BMI category (normal/overweight/obese) with activity status (active/inactive) using weekly vigorous activity as the threshold.

Results

After a median follow-up of 23.1 years, there were 1836 cases of incident diabetes. Compared with active participants with normal BMIs, active but overweight and obese men had multivariable-adjusted HRs of 2.39 (95% CI, 2.11-2.71) and 6.22 (95% CI, 5.12-7.56). Inactive men with normal, overweight, or obese BMIs had multivariable-adjusted HRs of 1.41 (95% CI, 1.19-1.67), 3.14 (95% CI, 2.73-3.62), and 6.57 (95% CI, 5.25-8.21).

Conclusion

Active men with normal and overweight BMIs had lower diabetes hazards than their inactive counterparts, but no difference by weekly activity was seen in obese men. Elevated BMI is a key driver of diabetes risk, with relatively modest attenuation by activity.     

甘精胰岛素联合二甲双胍在改善2型糖尿病患者胰岛功能中的应用

目的分析甘精胰岛素联合二甲双胍在改善2型糖尿病患者胰岛功能中的应用效果。方法 2017年3月-2018年8月在该中心遴选84例2型糖尿病患者,随机分为治疗组(n=42例)和对照组(n=42例),分别应用甘精胰岛素联合二甲双胍治疗、单独的甘精胰岛素治疗。比较两组疗效,观察空腹血糖等血糖指标和空腹胰岛素等胰岛功能指标的变化,记录不良反应。结果治疗组的总有效率为92.86%,比对照组的76.19%效率更高,差异有统计学意义(P<0.05);治疗组的不良反应发生率为11.9%,对照组为16.67%,差异无统计学意义(P>0.05)。结论甘精胰岛素联合二甲双胍在改善2型糖尿病患者胰岛功能中的应用临床效果显著。     

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.     

Insulin Therapy and Colorectal Adenoma Risk Among Patients with Type 2 Diabetes Mellitus: A Case-Control Study in Korea

Purpose Patients with Type 2 diabetes mellitus may be at increased colorectal adenoma and cancer risk. Moreover, chronic insulin therapy may increase the risk of colorectal cancer among patients with Type 2 diabetes mellitus. We investigated to determine whether insulin therapy might increase the risk of colorectal adenoma among clinically confirmed patients with Type 2 diabetes mellitus. Methods We conducted a retrospective study among patients with Type 2 diabetes mellitus who underwent total colonoscopy between January 2003 and July 2006 at Hallym University Sacred Heart Hospital. Among them (n = 325), patients with histologically confirmed colorectal adenomas (n = 100) and the same number of controls matched by age and sex were selected and analyzed. Results Adenoma cases showed significantly higher rate of chronic insulin therapy (more than 1 year) than controls (P = 0.018). In multivariate regression analysis, patients who received chronic insulin therapy had three times the risk of colorectal adenoma compared with patients who received no insulin (odds ratio, 3; 95 percent confidence interval, 1.1–8.9; P = 0.04). Conclusions Chronic insulin therapy was associated with increased colorectal adenoma risk among Type 2 diabetes mellitus patients. This result may provide a need for more intensive colorectal cancer screening program in patients with Type 2 diabetes mellitus, especially those who receive chronic insulin therapy.     

The Effect of Glycaemic Control and the Introduction of Insulin Therapy on Retinopathy in Non-insulin-dependent Diabetes Mellitus

To study the progression of diabetic retinopathy in relation to diabetes treatment and glycaemic control in patients with non-insulin dependent (Type 2) diabetes mellitus (NIDDM), we performed a prospective study in a cohort of 1378 diabetic patients, aged ⩾40 years at diagnosis, of whom 333 were treated with insulin, and 1045 with oral antihyperglycaemic agents or diet alone. In the latter group 174 patients changed to insulin therapy during follow-up. We used the Wisconsin scale to grade retinopathy, recorded blindness (visual acuity ⩽0.1) and visual impairment (visual acuity 0.2–0.4), and measured the average HbA_1c for each patient during a mean 3.1-year study period. In a multivariate analysis, patients who changed treatment from oral agents or diet alone to insulin therapy had a relative risk of 2.0 (95 % confidence interval 1.7–2.3) for progression of retinopathy ⩾3 levels compared with all other patients in the study. The increase in risk remained even after controlling for mean HbA_1c (relative risk 1.6; 95 % confidence interval 1.3–1.9). Progression ⩾3 levels was significantly associated with a higher incidence of macular oedema and deterioration of visual acuity (p < 0.001). The relative risk for blindness/visual impairment due to retinopathy was 2.7 (95 % confidence interval 1.8–4.0) in the group with changed treatment compared with all the other patients in the study. Poor glycaemic control (HbA_1c %) before the start of insulin therapy and any retinopathy at baseline were significant risk factors for progression in the group with changed treatment (both p < 0.01). In the whole study group, poor glycaemic control was significantly associated with retinopathy progression ⩾3 levels; the relative risk for those having mean HbA_1c above the median being 1.7 (95 % confidence interval 1.4–2.1), compared to those with a HbA_1c value below the median. Moderate non-proliferative diabetic retinopathy at baseline was also associated with progression (relative risk 2.5; 95 % confidence interval 1.4–4.5). In contrast, insulin treatment at baseline was not associated with an increased risk of retinopathy progression. In conclusion, while hyperglycaemia was a risk factor for the progression of retinopathy in all patients, change of treatment from oral drugs to insulin was associated with a 100 % increased risk of retinopathy progression and a 3-fold increased risk of blindness/visual impairment. © 1997 by John Wiley & Sons, Ltd.