A case study of type 2 diabetes self-management

Background  

It has been established that careful diabetes self-management is essential in avoiding chronic complications that compromise health. Disciplined diet control and regular exercise are the keys for the type 2 diabetes self-management. An ability to maintain one's blood glucose at a relatively flat level, not fluctuating wildly with meals and hypoglycemic medical intervention, would be the goal for self-management. Hemoglobin A1c (HbA1c or simply A1c) is a measure of a long-term blood plasma glucose average, a reliable index to reflect one's diabetic condition. A simple regimen that could reduce the elevated A1c levels without altering much of type 2 diabetic patients' daily routine denotes a successful self-management strategy.     

Insulin use and weight maintenance in well-controlled type 2 diabetes: a prospective cohort study

Intensification of glycemic control is associated with weight gain, however, less is known about weight change during the maintenance phase of glycemic management. On the basis of current models of energy homeostasis, we hypothesize that insulin use will result in less weight gain than oral antidiabetic agents in patients with well-controlled diabetes. This is a prospective cohort nested within a randomized control trial at an academic clinic, with enrollment from June 2002 to January 2005. A total of 163 patients with type 2 diabetes were enrolled after obtaining glycemic control. Insulin use was assessed by self-report at baseline. Participants were weighed at baseline and five follow-up visits over 24 months. The weight change was compared between insulin users and noninsulin users. The average (s.d.) age was 55 (11), 44% are female and 21% are black. The median duration of diabetes was 5 (0.5-10) years. At baseline, 88 participants (54%) reported insulin use with an average of 69 (6) units/day. Baseline BMI in the insulin users was 35 (6) and 33 (6) in noninsulin patients. Over 24 months, noninsulin patients gained 2.3 additional kilograms compared with insulin users (2.8 kg (6.8) vs. 0.5 kg (6.5), P = 0.065). After adjusting for age, race, sex, baseline weight, intervention status, and change in A1C, insulin users had 2.5 kg less weight gain than noninsulin users (P = 0.033). Less weight gain was observed over 24 months in insulin-treated patients. Whether this effect may be due to central catabolic effects of insulin merits additional confirmatory study and mechanistic investigation.     

Relation between psychosocial variables and the glycemic control of patients with type 2 diabetes: A cross-sectional and prospective study

Background  

This cross-sectional and prospective study used a variety of psychological inventories to evaluate the relationship between psychosocial factors and the glycemic control of patients with type 2 diabetes.     

New approaches in the treatment of type 2 diabetes

Type 2 diabetes is a chronic metabolic derangement that results from defects in both insulin action and secretion. New thiazolidinedione insulin sensitizers have been recently launched. New approaches with mechanisms different from current therapies are being explored, including novel ligands of peroxisome proliferator-activated receptor, glucagon receptor antagonists, dipeptidyl peptidase IV inhibitors, and insulin receptor activators.     

Vanadium treatment of type 2 diabetes: A view to the future

3-Hydroxy-2-methyl-4-pyrone and 2-ethyl-3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable as ligands for vanadyl ions, in potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use, and have undergone extensive pre-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL₂) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy. BEOV has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a range of doses from 10 mg to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects; all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020), 20 mg, daily for 28 days, per os, in seven type 2 diabetic subjects, was associated with reductions in fasting blood glucose and %HbA1c; improved responses to oral glucose tolerance testing, versus the observed worsening of diabetic symptoms in the two placebo controls.     

High-normal blood pressure and long-term risk of type 2 diabetes: 35-year prospective population based cohort study of men

Background

Atrial fibrillation is the most common type of arrhythmia after cardiac surgery. An increasing body of evidence demonstrates that oxidative stress plays a pivotal role in the pathophysiology of atrial fibrillation. N-acetylcysteine (NAC) is a free radical scavenger, and may attenuate this pathophysiologic response and reduce the incidence of postoperative AF (POAF). However, it is unclear whether NAC could effectively prevent POAF. Therefore, this meta-analysis aims to assess the efficacy of NAC supplementation on the prevention of POAF.

Methods

Medline and Embase were systematically reviewed for studies published up to November 2011, in which NAC was compared with controls for adult patients undergoing cardiac surgery. Outcome measures comprised the incidence of POAF and hospital length of stay (LOS). The meta-analysis was performed with the fixed-effect model or random-effect model according to the heterogeneity.

Results

Eight randomized trials incorporating 578 patients provided the best evidence and were included in this meta-analysis. NAC supplementation significantly reduced the incidence of POAF (OR 0.62, 95% CI 0.41 to 0.93; P = 0.021) compared with controls, but had no effect on LOS (WMD -0.07, 95% CI -0.42 to 0.28; P = 0.703).

Conclusions

The prophylactic NAC supplementation may effectively reduce the incidence of POAF. However, the overall quality of current studies is poor and further research should focus on adequately powered randomized controlled trials with POAF incidence as a primary outcome measure.     

Toenail selenium and risk of type 2 diabetes: the ORDET cohort study

Epidemiologic studies, particularly randomized controlled trials, have shown a direct relation between dietary and environmental exposure to the metalloid selenium and risk of type 2 diabetes. We investigated the association between baseline toenail selenium levels and diabetes occurrence in a case–control study nested in ORDET, a population-based female cohort in Northern Italy. After a median follow-up of 16 years, we identified 226 cases of type 2 diabetes cases and 395 age-matched control women with available toenail samples at baseline. The multivariate odds ratios of diabetes in increasing a priori defined categories of toenail selenium exposure were 1.09 (95% confidence interval 0.61, 1.96), 0.71 (0.38, 1.34) and 1.14 (0.46, 2.80) compared with the lowest category. The results were not substantially altered when quartile distribution of toenail selenium in controls was used to define exposure categories. Spline regression analysis did not show homogeneous risk trends. Overall, we did not find an association between toenail selenium and subsequent development of diabetes. Since the diabetogenic activity of selenium is strongly supported by experimental studies and some observational investigations, our null results might be explained by the limitations of overall selenium toenail content to assess environmental exposure to selenium species of etiologic relevance in the study population.     

Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands

Objective To investigate maternal, perinatal, and neonatal outcomes of pregnancies in women with type 1 diabetes in the Netherlands.Design Nationwide prospective cohort study.Setting All 118 hospitals in the Netherlands.Participants 323 women with type 1 diabetes who became pregnant between 1 April 1999 and 1 April 2000.Main outcome measures Maternal, perinatal, and neonatal outcomes of pregnancy.Results 84% (n = 271) of the pregnancies were planned. Glycaemic control early in pregnancy was good in most women (HbA_1c ≤ 7.0% in 75% (n = 212) of the population), and folic acid supplementation was adequate in 70% (n = 226). 314 pregnancies that went beyond 24 weeks'' gestation resulted in 324 infants. The rates of pre-eclampsia (40; 12.7%), preterm delivery (101; 32.2%), caesarean section (139; 44.3%), maternal mortality (2; 0.6%), congenital malformations (29; 8.8%), perinatal mortality (9; 2.8%), and macrosomia (146; 45.1%) were considerably higher than in the general population. Neonatal morbidity (one or more complications) was extremely high (260; 80.2%). The incidence of major congenital malformations was significantly lower in planned pregnancies than in unplanned pregnancies (4.2% (n = 11) v 12.2% (n = 6); relative risk 0.34, 95% confidence interval 0.13 to 0.88).Conclusion Despite a high frequency of planned pregnancies, resulting in overall good glycaemic control (early) in pregnancy and a high rate of adequate use of folic acid, maternal and perinatal complications were still increased in women with type 1 diabetes. Neonatal morbidity, especially hypoglycaemia, was also extremely high. Near optimal maternal glycaemic control (HbA_1c ≤ 7.0%) apparently is not good enough.     

Prevention and treatment of type 2 diabetes in youth

Parallel to the increase in obesity worldwide, there has been a rise in the prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents. The etiology of T2DM in youth, similar to adults, is multifactorial including genetic and environmental factors, among them obesity, sedentary lifestyle, family history of the disease, high-risk ethnicity and insulin resistance phenotype playing major roles. Treatment of T2DM should not have a glucocentric approach; it should rather target improving glycemia, dyslipidemia, hypertension, weight management and the prevention of short- and long-term complications. Prevention strategies, especially in high-risk groups, should focus on environmental change involving participation of families, schools, the food and entertainment industries and governmental agencies. Presently, limited pharmacotherapeutic options need to be expanded both for childhood T2DM and obesity. The coming decades will prove very challenging for healthcare providers battling socioeconomic waves conducive to obesity and T2DM. Evidence-based research and clinical experience in pediatrics, possibly modeled after adult trials, need to be developed if this public health threat is to be contained.     

Obesity and the relation between joint exposure to ambient air pollutants and incident type 2 diabetes: A cohort study in UK Biobank

BackgroundAir pollution has been related to incidence of type 2 diabetes (T2D). We assessed the joint association of various air pollutants with the risk of T2D and examined potential modification by obesity status and genetic susceptibility on the relationship.Methods and findingsA total of 449,006 participants from UK Biobank free of T2D at baseline were included. Of all the study population, 90.9% were white and 45.7% were male. The participants had a mean age of 56.6 (SD 8.1) years old and a mean body mass index (BMI) of 27.4 (SD 4.8) kg/m². Ambient air pollutants, including particulate matter (PM) with diameters ≤2.5 μm (PM_2.5), between 2.5 μm and 10 μm (PM_2.5–10), nitrogen dioxide (NO₂), and nitric oxide (NO) were measured. An air pollution score was created to assess the joint exposure to the 4 air pollutants. During a median of 11 years follow-up, we documented 18,239 incident T2D cases. The air pollution score was significantly associated with a higher risk of T2D. Compared to the lowest quintile of air pollution score, the hazard ratio (HR) (95% confidence interval [CI]) for T2D was 1.05 (0.99 to 1.10, p = 0.11), 1.06 (1.00 to 1.11, p = 0.051), 1.09 (1.03 to 1.15, p = 0.002), and 1.12 (1.06 to 1.19, p < 0.001) for the second to fifth quintile, respectively, after adjustment for sociodemographic characteristics, lifestyle factors, genetic factors, and other covariates. In addition, we found a significant interaction between the air pollution score and obesity status on the risk of T2D (p-interaction < 0.001). The observed association was more pronounced among overweight and obese participants than in the normal-weight people. Genetic risk score (GRS) for T2D or obesity did not modify the relationship between air pollution and risk of T2D. Key study limitations include unavailable data on other potential T2D-related air pollutants and single-time measurement on air pollutants.ConclusionsWe found that various air pollutants PM_2.5, PM_2.5–10, NO_2, and NO, individually or jointly, were associated with an increased risk of T2D in the population. The stratified analyses indicate that such associations were more strongly associated with T2D risk among those with higher adiposity.

Xiang Li and co-workers study the potential influence of obesity on associations between air pollutants and incidence of type 2 diabetes.     

Thermal biofeedback in the treatment of intermittent claudication in diabetes: A case study

The objective of the present case study was to examine the therapeutic effects of thermal biofeedback-assisted autogenic training on a patient with non-insulin-dependent diabetes mellitus (NIDDM), vascular disease, and symptoms of intermittent claudication. The patient received thermal biofeedback from the hand for five sessions, then from the foot for 16 sessions, while hand and foot skin temperature were monitored simultaneously. In addition, the patient was instructed in autogenic training and practiced daily at home. Follow-up measurements were taken at 12 and 48 months. Within-session foot temperature rose specifically in response to foot temperature biofeedback and starting foot temperature rose between sessions. Posttreatment blood pressure was reduced to a normal level. Attacks of intermittent claudication were reduced to zero after 12 sessions and walking distance increased by about a mile per day over the course of treatment. It would appear that thermal biofeedback and autogenic training are potentially promising therapies for persons with diabetes and peripheral vascular disease.Preparation of this article was supported in part by NIDDK grant No. R0128288 and the Commonwealth of Virginia Diabetes Clinical Research Institute.     

Heat shock protein 70 and albuminuria in patients with type 2 diabetes: a matched case control study

Here, we aimed to study serum heat shock protein (HSP) 70 levels in diabetic patients with and without albuminuria. We performed a 1:1 matched case control study on 40 diabetic patients with albuminuria as cases and 40 age, sex, body mass index matched diabetic patients without albuminuria (normoalbuminuria) as controls. Normoalbuminuria was defined as urinary albumin excretion rate <15 mg/12 h, and albuminuria was defined as urinary albumin excretion rate between 100–400 mg/12 h. Patients with albuminuria had a higher HSP70 than controls (0.83 ± 0.50 vs. 0.63 ± 0.06; p = 0.02), while they did not differ in any other studied variables. In ten of the studied pairs, the controls had higher HSP70 levels than cases (reverse relationship). Patients in the “direct relationship group” had higher HbA1c values than the patients in the “reverse relationship group” (8.9 ± 0.3 vs. 7.3 ± 0.6, p = 0.04). Cases in the reverse pairs had a lower low density lipoprotein cholesterol levels than their controls. The odds ratio of HSP70 in the prediction of albuminuria was (28.69 (3.2–250.1), p = 0.002). In conclusion, we have shown an increased HSP70 levels in diabetic patients with albuminuria.     

Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study

ObjectiveTo determine the relation between systolic blood pressure over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.DesignProspective observational study.Setting23 hospital based clinics in England, Scotland, and Northern Ireland.Participants4801 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk.ResultsThe incidence of clinical complications was significantly associated with systolic blood pressure, except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes (95% confidence interval 10% to 14%, P<0.0001), 15% for deaths related to diabetes (12% to 18%, P<0.0001), 11% for myocardial infarction (7% to 14%, P<0.0001), and 13% for microvascular complications (10% to 16%, P<0.0001). No threshold of risk was observed for any end point.ConclusionsIn patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised blood pressure. Any reduction in blood pressure is likely to reduce the risk of complications, with the lowest risk being in those with systolic blood pressure less than 120 mm Hg.     

The role of melatonin in the treatment of type 2 diabetes mellitus and Alzheimer's disease

In type 2 diabetes mellitus (T2DM) and its related disorders like obesity, the abnormal protein processing, oxidative stress and proinflammatory cytokines will drive the activation of inflammatory pathways, leading to low-grade chronic inflammation and insulin resistance (IR) in the periphery and impaired neuronal insulin signaling in the brain. Studies have shown that such inflammation and impaired insulin signaling contribute to the development of Alzheimer''s disease (AD). Therefore, new therapeutic strategies are needed for the treatment of T2DM and T2DM-linked AD. Melatonin is primarily known for its circadian role which conveys message of darkness and induces night-state physiological functions. Besides rhythm-related effects, melatonin has anti-inflammatory and antioxidant properties. Melatonin levels are downregulated in metabolic disorders with IR, and activation of melatonin signaling delays disease progression. The aim of this Review is to highlight the therapeutic potentials of melatonin in preventing the acceleration of AD in T2DM individuals through its therapeutic mechanisms, including antioxidative effects, anti-inflammatory effects, restoring mitochondrial function and insulin sensitivity.     

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease.