Hyperinsulinemia—How Innocent a Bystander?

Abstract

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.

Leptin and other components of the Metabolic Syndrome in Mauritius—a factor analysis

“…It is not clear why fasting insulin was not as important as 2 h insulin in the glucose intolerance factor, but this observation agrees with that of Meigs et al, 17 who suggest that elevated 2 h insulin re¯ects both peripheral insulin resistance and inadequate early insulin response. 2 Fasting insulin on the other hand, was more closely related to factor 1, characterized by adiposity, lipid levels and leptin. Fasting insulin is closely correlated with insulin resistance as measured by clamp studies, and is generally considered to be the better marker of insulin resistance for epidemiologic studies.…”

“…Glucose tolerance status was classi®ed according to WHO recommendations. 16 Body mass index (BMI) was calculated as kgam 2 and waist and hip girth were measured in duplicate to calculate waista hip ratio (WHR) from the means of measurements as previously described. 14 Eligibility for the present study was limited to 1414 men and 1654 women who were non-diabetic (normal and impaired glucose tolerance) in 1987, and who also attended a follow-up survey in 1992, as leptin measurements were only done on sera frozen since 1987 (À20 C) in subjects who attended both surveys.…”

“…1 Hyperuricaemia, and microalbuminuria are sometimes included in the syndrome. 2 It is generally believed that hyperinsulinaemia andaor insulin resistance underlie this clustering. 1 Leptin, the product of the ob gene, has been observed to be closely correlated with insulin levels, independently of obesity, in a range of populations; 3 and in a study of Polynesian Samoans was also independently associated with key variables of the Metabolic Syndrome.…”

Can supplementary dietary fibre suppress breast cancer growth?

“…Stimulation of breast cancer growth may involve synergism between oestradiol and insulin-like growth factor 1 in a mitogenic effect on breast tissue (Stewart et al, 1990). A tendency to insulin resistance is genetically determined but can be triggered by a fat-rich diet (Zimmet, 1993). Insulin resistance is commonly associated with an elevated level of bioavailable oestrogen (Bruning et al, 1992), and this observation has prompted the hypothesis that breast cancer may be promoted at critical times in a woman's life by the metabolic/endocrine abnormality (Stoll, 1995).…”

The Effect of Dietary Energy Restriction on Body Weight Gain and the Development of Noninsulin‐Dependent Diabetes Mellitus (NIDDM) in Psammomys obesus

“…The disease results from a complex interaction between genetic and environmental factors, and often forms part of the common metabolic cluster known as Syndrome X (34) or the Metabolic Syndrome (43), which also includes obesity and other cardiovascular risk factors.…”