This statement examines the cardiovascular complications of diabetes mellitus and considers opportunities for their prevention. These complications include coronary heart disease (CHD), stroke, peripheral arterial disease, nephropathy, retinopathy, and possibly neuropathy and cardiomyopathy. Because of the aging of the population and an increasing prevalence of obesity and sedentary life habits in the United States, the prevalence of diabetes is increasing. Thus, diabetes must take its place alongside the other major risk factors as important causes of cardiovascular disease (CVD). In fact, from the point of view of cardiovascular medicine, it may be appropriate to say, “diabetes is a cardiovascular disease.”

The most prevalent form of diabetes mellitus is type 2 diabetes. This disorder typically makes its appearance later in life. The underlying metabolic causes of type 2 diabetes are the combination of impairment in insulin-mediated glucose disposal (insulin resistance) and defective secretion of insulin by pancreatic β-cells. Insulin resistance develops from obesity and physical inactivity, acting on a substrate of genetic susceptibility.1 2 Insulin secretion declines with advancing age,3 4 and this decline may be accelerated by genetic factors.5 6 Insulin resistance typically precedes the onset of type 2 diabetes and is commonly accompanied by other cardiovascular risk factors: dyslipidemia, hypertension, and prothrombotic factors.7 8 The common clustering of these risk factors in a single individual has been called the metabolic syndrome. Many patients with the metabolic syndrome manifest impaired fasting glucose (IFG)9 even when they do not have overt diabetes mellitus.10 The metabolic syndrome commonly precedes the development of type 2 diabetes by many years11 ; of great importance, the risk factors that constitute this syndrome contribute independently to CVD risk.

Recently, new criteria have been accepted for the diagnosis of diabetes.9 The upper threshold of fasting plasma glucose for the …

https://cdr.lib.unc.edu/downloads/m900nw482

Diabetes and cardiovascular disease : A statement for healthcare professionals from the American heart association

Prevention and control programmes are needed to stem the rising epidemic of diabetes and its complications. However, these will not occur unless governments and public health planners are aware of the potential problem. Using published prevalence rates for NIDDM in different populations, and the current and projected age distributions, worldwide prevalence of NIDDM was estimated for 1995 and 1997, and well as projections for 2000 and 2010. Prevalence rates used for projections were chosen to reflect changes in lifestyle with economic development. The global prevalence of IDDM was estimated using published incidence rates and population figures, incorporating the likely survival time from development of IDDM. Data on diabetes complications are also summarised but no attempt has been made to extrapolate to a global estimated. In 1997, an estimated 124 million people worldwide have diabetes, 97% of these having NIDDM. By the year 2010 the total number of people with diabetes is projected to reach 221 million. The regions with the greatest potential increases are Asia and Africa, where diabetes rates could rise to 2 or 3 times those experienced today. With improvements in the treatment of IDDM, the prevalence of this form of diabetes is likely to increase as more people survive for longer after diagnosis. Increases in complications will undoubtedly follow increasing prevalence of diabetes, but population-based studies using standardised methods of diagnosis are required before reliable estimates of the extent of the problem can be made. It is hoped that the information provided in this report, and others like it, will act as an incentive to initiate or improve local diabetes monitoring and prevention strategies.

The Rising Global Burden of Diabetes and its Complications: Estimates and Projections to the Year 2010

https://www.kidney-international.org/article/S0085-2538(15)55004-7/pdf

The contribution of chronic kidney disease to the global burden of major noncommunicable diseases

Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Islington Diabetes Survey.

Diabetes mellitus and hypertension are common diseases that coexist at a greater frequency than chance alone would predict. Hypertension in the diabetic individual markedly increases the risk and accelerates the course of cardiac disease, peripheral vascular disease, stroke, retinopathy, and nephropathy. Our understanding of the factors that markedly increase the frequency of hypertension in the diabetic individual remains incomplete. Diabetic nephropathy is an important factor involved in the development of hypertension in diabetics, particularly type I patients. However, the etiology of hypertension in the majority of diabetic patients cannot be explained by underlying renal disease and remains "essential" in nature. The hallmark of hypertension in type I and type II diabetics appears to be increased peripheral vascular resistance. Increased exchangeable sodium may also play a role in the pathogenesis of blood pressure in diabetics. There is increasing evidence that insulin resistance/hyperinsulinemia may play a key role in the pathogenesis of hypertension in both subtle and overt abnormalities of carbohydrate metabolism. Population studies suggest that elevated insulin levels, which often occurs in type II diabetes mellitus, is an independent risk factor for cardiovascular disease. Other cardiovascular risk factors in diabetic individuals include abnormalities of lipid metabolism, platelet function, and clotting factors. The goal of antihypertensive therapy in the patient with coexistent diabetes is to reduce the inordinate cardiovascular risk as well as lowering blood pressure.

Diabetes mellitus and hypertension.

Diabetic nephropathy is the main cause of the increased morbidity and mortality in patients with insulin dependent diabetes. The prevalence of microalbuminuria was determined in adults with insulin dependent diabetes of five or more years9 duration that had started before the age of 41. All eligible patients (n=982) attending a diabetes clinic were asked to collect a 24 hour urine sample for analysis of albumin excretion by radio-immunoassay; 957 patients complied. Normoalbuminuria was defined as urinary albumin excretion of ≤30 mg/24 h (n=562), microalbuminuria as 31-299 mg/24 h (n=215), and macroalbuminuria as ≥300 mg/24 h (n=180). The prevalence of microalbuminuria and macroalbuminuria was significantly higher in patients whose diabetes had developed before rather than after the age of 20. The prevalence of arterial hypertension increased with increased albuminuria, being 19%, 30%, and 65% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. The prevalence of proliferative retinopathy and blindness rose with increasing albuminuria, being 12% and 1·4%, respectively, in patients with normoalbuminuria, 28% and 5·6% in those with microalbuminuria and 58% and 10·6% in those with macroalbuminuria. An abnormal vibratory perception threshold was more common in patients with microalbuminuria (31%) and macroalbuminuria (50%) than in those with normoalbuminuria (21%). This study found a high prevalence (22%) of microalbuminuria, which is predictive of the later development of diabetic nephropathy. Microalbuminuria is also characterised by an increased prevalence of arterial hypertension, proliferative retinopathy, blindness, and peripheral neuropathy. Thus, urinary excretion of albumin should be monitored routinely in patients with insulin dependent diabetes.

/pdf/prevalence-of-microalbuminuria-arterial-hypertension-3pqrihqv8t.pdf

Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes

Context Hypothalamic injury often leads to rapid, intractable weight gain causing hypothalamic obesity, which is associated with increased risk of cardiovascular and metabolic morbidity and mortality. There are no approved or effective pharmacological treatments for hypothalamic obesity, and conventional lifestyle management remains ineffective. Objective To investigate the safety and efficacy of Tesomet (0.5 mg tesofensine/50 mg metoprolol) in adults with hypothalamic obesity. Methods Twenty-one adults with hypothalamic obesity (16 females) were randomized to Tesomet (0.5 mg/50 mg) or placebo for 24 weeks. Patients also received diet/lifestyle counselling. The primary endpoint was safety; secondary endpoints included measures of body weight, appetite scores, quality of life, and metabolic profile. Results Eighteen patients completed 24 weeks. Consent withdrawal, eligibility, and serious adverse events (SAE) unrelated to treatment resulted in dropouts. One patient experienced a Tesomet-related SAE of exacerbated pre-existing anxiety leading to treatment discontinuation. Tesomet-related adverse events were otherwise mostly mild and included sleep disturbances (Tesomet 50%, placebo 13%), dry mouth (Tesomet 43%, placebo 0%), and headache (Tesomet 36%, placebo 0%). No significant differences in heart rate or blood pressure were observed between groups. Compared to placebo, Tesomet resulted in additional mean (95% CI) weight change of −6.3% ((−11.3; −1.3); P  = 0.017), increased the number of patients achieving ≥5% weight loss (Tesomet 8/13, placebo 1/8; P  = 0.046), and tended to augment the reduction in waist circumference by 5.7 cm ((−0.1; 11.5); P  = 0.054). Conclusion Tesomet was welltolerated, did not affect heart rate or blood pressure, and resulted in significant reductions in body weight compared to placebo in adults with hypothalamic obesity.

https://eje.bioscientifica.com/downloadpdf/journals/eje/aop/eje-21-0972/eje-21-0972.pdf

Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity

Abstract Objective To assess the safety and efficacy of Tesomet (tesofensine plus metoprolol) in adults with hypothalamic obesity, a rare disease with no approved therapy. Research Design and Methods Twenty-one adults with hypothalamic obesity (16 females, 5 males) were randomized to Tesomet (0.5 mg tesofensine/50 mg metoprolol) (n=14) or placebo (n=8) during a 24-week double-blind period. On completion of the double-blind period, 17 (81%) subjects (11 Tesomet; 6 placebo) entered in to a 24-week open-label extension period and were treated with Tesomet. The primary endpoint was safety while secondary endpoints included measures of body weight, waist circumference, and body composition. Trial NCT03845075. Results The most common adverse events following the 24-week double-blind period and the 24-week open-label extension period were sleep disorder, dizziness, dry mouth, and headache; the majority of these adverse events were mild to moderate in severity. No significant nor clinically meaningful changes in heart rate or blood pressure were observed during the study. On completion of the double-blind period mean change in body weight (kg) was -7.84 for the Tesomet group versus -0.34 kg for the placebo group (P=0. 03). At the end of the open-label extension period mean change in body weight (kg) from baseline was -6.34 for the Tesomet-Tesomet group and -6. 03 for the placebo-Tesomet group. On completion of the double-blind period mean change in waist circumference (cm) was -7. 09 cm for the Tesomet group versus -1.16 for the placebo group (P=NS). At the end of the open-label extension period mean change in waist circumference (cm) from baseline was -5.73 for the Tesomet-Tesomet group and -3. 04 for the placebo-Tesomet group. On completion of the double-blind period mean change in fat mass (kg) was -5.28 for the Tesomet group versus -1.11 for the placebo group (P=NS). At the end of the open-label extension period mean change in fat mass (kg) from baseline was -4.84 for the Tesomet-Tesomet group and -3.85 for the placebo-Tesomet group. On completion of the double-blind period mean change in lean tissue mass (kg) was -2.76 for the Tesomet group versus 0.36 for the placebo group (P<0. 01). At the end of the open-label extension period mean change in lean mass (kg) from baseline was -1.64 for the Tesomet-Tesomet group and -2.22 for the placebo-Tesomet group. Discussion Tesomet was generally well tolerated after 48 weeks treatment and resulted in clinically meaningful improvements in body weight and body composition measures in adults with hypothalamic obesity. In contrast to previous studies of tesofensine monotherapy in general obesity, no significant nor clinically meaningful changes in cardiovascular measures were observed during the study. Conclusion Tesomet is a promising new experimental treatment for hypothalamic obesity. A randomized, placebo controlled, multi-center, dose-finding, Phase 2b study has now been initiated. Presentation: No date and time listed

/pdf/odp350-safety-and-efficacy-of-tesomet-over-48-weeks-of-282wq8i3.pdf

ODP350 Safety and Efficacy of Tesomet over 48 Weeks of Treatment: Results From a 24-Week Phase 2, Randomized, Double-Blind Study With 24 Week Open-Label Extension in Adults With Hypothalamic Obesity

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online) 

Significant weight loss resulted in reduced levothyroxine requirements during a tesomet trial of hypopituitary patients with acquired hypothalamic obesity

Berit Edsberg

Papers

Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes

Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity

ODP350 Safety and Efficacy of Tesomet over 48 Weeks of Treatment: Results From a 24-Week Phase 2, Randomized, Double-Blind Study With 24 Week Open-Label Extension in Adults With Hypothalamic Obesity

Significant weight loss resulted in reduced levothyroxine requirements during a tesomet trial of hypopituitary patients with acquired hypothalamic obesity