Treatment of Severe Diabetes Mellitus by Insulin Infusion

A new and simple form of insulin therapy for diabetic hyperglycaemia and ketoacidosis has been developed using a continuous intravenous infusion of insulin at a rate of 2·4 U/hr to maintain serum insulin concentration at physiological levels. This rate raises the mean serum insulin to 83 μU/ml and has a therapeutic effect which is not augmented by higher infusion rates. The response to such low doses of insulin indicates a need for a reappraisal of currently held theories about insulin resistance in diabetic ketoacidosis. In 11 diabetic patients with a mean plasma glucose of 514 mg/100 ml this therapy produced continuous falls in plasma glucose at a mean rate of 75 mg/100 ml/hr, and 10 out of 11 patients recovered within eight hours. This form of therapy is simple to institute, not complicated by hypoglycaemia, and avoids the confusion and empiricism of previously described forms of therapy.     

Serum Glycated Albumin to Guide the Diagnosis of Diabetes Mellitus

In the diagnosis of diabetes mellitus, hemoglobin A1c (HbA1c) is sometimes measured to determine the need of an oral glucose tolerance test (OGTT). However, HbA1c does not accurately reflect glycemic status in certain conditions. This study was performed to test the possibility that measurement of serum glycated albumin (GA) better assesses the need for OGTT. From 2006 to 2012, 1559 subjects not known to have diabetes or to use anti-diabetic medications were enrolled. Serum GA was measured, and a 75-g OGTT was then performed to diagnose diabetes. Serum GA correlated significantly to age (r = 0.27, p<0.001), serum albumin (r = –0.1179, age-adjusted p = 0.001), body mass index (r = -0.24, age-adjusted p<0.001), waist circumference (r = -0.16, age-adjusted p<0.001), and plasma GA (r = 0.999, p<0.001), but was unaffected by diet (p = 0.8). Using serum GA at 15% for diagnosis of diabetes, the sensitivity, specificity, and area under the receiver-operating characteristic curve were 74%, 85%, and 0.86, respectively. Applying a fasting plasma glucose (FPG) value of < 100 mg/dL to exclude diabetes and of ≥ 126 mg/dL to diagnose diabetes, 14.4% of the study population require an OGTT (OGTT%) with a sensitivity of 78.8% and a specificity of 100%. When serum GA value of 14% and 17% were used to exclude and diagnose diabetes, respectively, the sensitivity improved to 83.3%, with a slightly decrease in specificity (98.2%), but a significant increase in OGTT% (35%). Using combined FPG and serum GA cutoff values (FPG < 100 mg/dL plus serum GA < 15% to exclude diabetes and FPG ≥ 126 mg/dL or serum GA ≥ 17% to diagnose diabetes), the OGTT% was reduced to 22.5% and the sensitivity increased to 85.6% with no change in specificity (98.2%). In the diagnosis of diabetes, serum GA measurements can be used to determine the need of an OGTT.     

罗格列酮联合胰岛素治疗老年2型糖尿病的临床研究

目的 观察罗格列酮联合胰岛素治疗老年2型糖尿病的疗效及安全性.方法 将60例老年2型糖尿病患者随机分为治疗组和对照组各30例,治疗组用罗格列酮4 mg/d,同时加用胰岛素;两组均随访12周,观测血糖、胰岛素用量指标变化及药物的不良反应;对照组单用胰岛素治疗并根据病情调整用量.结果 治疗组血糖水平从第2周开始明显下降,第8～12周血糖水平降幅最大,有21例达到空腹血糖＜6.5 mmol/L,餐后2 h血糖＜8.0 mmol/L的良好控制水平;从第2周开始,治疗组胰岛素用量也逐渐减少,至12周时,治疗组胰岛素用量较基础值减少(7.6±4.3)u;而对照组胰岛素用量却平均增加(9.1±5.1)u.治疗后两组血糖和胰岛素用量比较差异有统计学意义(P＜0.05).结论 罗格列酮联合胰岛素治疗老年2型糖尿病能有效控制患者的血糖水平,且安全,无不良反应.     

Quality of Life and Insulin Therapy in Type 2 Diabetes Mellitus

Background: A frequently cited barrier to insulin use in type 2 diabetes mellitus (DM) is concern about the adverse effects on quality of life. Results of studies in this area have been mixed, with insulin use showing decreased, enhanced, or no impact on quality of life.Objective: The purpose of this paper is to discuss the state of the science regarding the effects of insulin on quality of life and to present strategies providers can implement in their clinical practices to decrease barriers to insulin use among patients with type 2 DM.Methods: An English-language MEDLINE search of the current literature using the terms insulin and quality of life was conducted for this article.Results: Although patient-identified concerns regarding insulin use represent some aspects of quality of life, study results have been mixed. However, 2 large studies examining the use of insulin glargine and its effects on quality of life found that glargine was associated with significantly greater improvements in quality of life when added to oral antidiabetic agents (OADs) than was the use of OADs alone. Another study examined the effects of intensive multi- therapy (monthly visits, self-management diabetes education, and medication adjustments) on quality of life among patients with type 2 DM and found that quality-of-life scores improved among patients who initiated insulin therapy during the trial. The effects of insulin delivery systems on quality of life have also been assessed. In these studies, patients preferred insulin pens over vials and syringes and inhaled over injected insulin. Health care providers can facilitate acceptance of insulin by employing strategies to help patients overcome psychological barriers to insulin therapy.Conclusions: Although patient concerns about the effects of insulin use are legitimate, insulin therapy is often needed to achieve treatment targets. Providers can reduce the impact on quality of life by addressing barriers, helping patients improve metabolic control, and providing ongoing information and support.     

Effect of Diabetes Mellitus on the Permeability of the Blood–Brain Barrier to Insulin

Banks, W. A., J. B. Jaspan and A. J. Kastin. Effect of diabetes mellitus on the permeability of the blood–brain barrier to insulin. Peptides 18(10) 1577–1584, 1997.—Insulin derived from the peripheral circulation has been shown to exert various effects on the brain due to its ability to cross the blood–brain barrier (BBB). The relation between diabetes mellitus and insulin has been extensively studied for peripheral tissues but not for central nervous system tissues. We examined the effects that streptozotocin- or alloxan-induced diabetes have on the transport of insulin across the murine BBB. We used multiple-time regression analysis to measure the unidirectional influx rate constant (K_i) and vascular association (V_i) of intravenously injected, radioactively labeled human insulin (I-Ins). Treatment with streptozotocin induced an enhancement of both the K_i and V_i of I-Ins that correlated with the onset of diabetes. Brain perfusion showed that the enhanced uptake was not due to altered vascular space or levels of insulin in the serum. Alloxan enhanced K_i and V_i after 5 days but the early phase of diabetes was associated with a decreased K_i. Hyperglycemia induced by the intraperitoneal injection of glucose elevated the V_i but abolished the K_i. Furthermore, altered I-Ins uptake by brain was not associated with changes in brain or body weight. These results show that there is an increased uptake of I-Ins by the brain in the diabetic state that is not due to acute changes in the serum levels of glucose or insulin, altered vascular space, or catabolic events. Chronic changes in levels of glucose, insulin or other hormone or neuroendocrine agents are likely to underlie the altered rate of transport of insulin across the BBB of diabetic mice.     

Metformin versus Insulin in the Management of Pre-Gestational Diabetes Mellitus in Pregnancy and Gestational Diabetes Mellitus at the Korle Bu Teaching Hospital: A Randomized Clinical Trial

ObjectiveTo determine if metformin monotherapy or metformin in combination with insulin is equally effective as insulin monotherapy at glycemic control in diabetes mellitus in pregnancy among Ghanaians.MethodsThis was a study involving 104 pregnant women with type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM) at 20-30 weeks gestation. Participants were randomized into metformin and insulin treatment groups. Starting dose of metformin was 500 mg once a day and increased gradually over two (2) weeks, to meet glycemic targets. Insulin was added if targets could not be reached on metformin alone at maximum doses. Total daily dose of premixed insulin at initiation was calculated as 0.3 IU/kg body weight and titrated upwards to achieve glycemic control. Glycemic profile monitoring was done every two weeks.ResultsThe two hour post prandial blood glucose (2HPG) levels were significantly lower in the metformin group than the insulin group (p= 0.004).ConclusionThe findings of this study suggest that metformin monotherapy is effective in achieving glycemic targets in the management of diabetes in pregnancy. It is more effective than insulin in lowering the 2HPG level.

Trial Registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12614000942651     

Higher Fetal Insulin Resistance in Chinese Pregnant Women with Gestational Diabetes Mellitus and Correlation with Maternal Insulin Resistance

Objective

The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM.

Measurements

Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function) were calculated in maternal and cord blood respectively.

Results

Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively). Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019), in the pregnant women with GDM.

Conclusions

Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.