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The metabolic syndrome is a combination of metabolic and clinical features that aggregate in individuals and increase cardiovascular disease (CVD) risk considerably. It is believed, although sometimes controversially, that the underlying basis for this syndrome is insulin resistance (IR) and accompanying compensatory hyperinsulinemia. Insulin and insulin-like growth factors (IGFs) have significant homology and interact with differing affinity with the same receptors. Therefore, their actions can be complementary, and this becomes particularly significant clinico-pathologically when their circulating levels are altered. This review of currently available information attempts to answer the following questions: (1) Is there any evidence for changes in the components of the IGF system in individuals with established CVD or with increased CVD risk as with the metabolic syndrome? (2) What are the underlying mechanisms for interactions, if any, between insulin and the IGF system, in the genesis of CVD? (3) Can knowledge of the pathophysiological changes in the IGF system observed in macrosomic newborn infants and growth hormone (GH)-treated children and adults explain some of the observations in relation to the IGF system and the metabolic syndrome? (4) Can the experimental and clinical evidence adduced from the foregoing be useful in designing novel therapies for the prevention, treatment, and assignment of prognosis in metabolic syndrome-associated disease, particularly ischemic heart disease? To answer these questions, we have performed a literature review using bibliographies from PubMed, Medline, and Google Scholar published within the last 10 years. We suggest that IGF-1 levels are reduced consistently in individuals with the metabolic syndrome and its components and in those with ischemic CVD. Such changes are also seen with GH deficiency in which these changes are partially reversible with GH treatment. Furthermore, changes are seen in levels and interactions of IGF-binding proteins in these disorders, and some of these changes appear to be independent of IGF-binding capability and could potentially impact on risk for the metabolic syndrome and CVD. The promising therapeutic implications of these observations are also discussed.

Serum lipoprotein(a) [Lp(a)], a risk factor for coronary heart disease (CHD) in some nondiabetic populations, is largely under genetic control and varies among ethnic and racial groups. We evaluated serum Lp(a) concentration and its relationship with traditional CHD risk factors (age, sex, smoking, hypertension, dyslipidemia) as well as stage of diabetic nephropathy in 345 type 2 diabetic patients. Lp(a) concentration was skewed with median (2.5th, 97.5th percentiles) of 25.0 (8.1, 75.7) mg/dl. Twenty-three of 55 (41.8%) patients with CHD had increased (>30 mg/dl) Lp(a) compared with 102 of 290 (35.1%) patients without CHD (P=.35). Twelve of 27 (44.4%) female patients with CHD had increased Lp(a) compared to 11 of 28 (39.3%) males (P=.70). Lp(a) was significantly (P<.05) higher in females than males, but the logistic regression analysis showed significant association of Lp(a), LDL-C, and duration of diabetes mellitus (DM) with CHD in male patients only. Although female patients with CHD and macroalbuminuria had significantly (P<.05) higher Lp(a) than normoalbuminuric female patients without CHD, no such association was found in males and no significant association was found between Lp(a) and the degree of albuminuria. Partial correlation analysis controlling for age, sex, and BMI showed significant correlation of Lp(a) with total cholesterol only (P=.03) and no correlation was found with other lipid parameters. Multiple regression analysis did not show significant associations of Lp(a) with standard CHD risk factors, HbA(1c), and plasma creatinine. This study is in agreement with studies in other populations, which showed that Lp(a) may not be an independent risk factor for CHD in patients with DM. However, as Lp(a) could promote atherogenesis via several mechanisms, follow-up studies in our patients will confirm if increased Lp(a) concentration can partly account for the poorer prognosis when diabetic patients develop CHD.

Serum total sialic acid is a marker of the acute phase response. Elevated levels have also been associated with cardiovascular disease in the general Caucasian population and especially in Type 2 diabetic subjects. The purpose of this study was to estimate serum total sialic acid concentrations among Kuwaiti Type 2 diabetic subjects and to investigate its association with macro and microvascular diabetes-related complications in that population. Serum total sialic acid levels were estimated by an enzymatic spectro-photometric assay in two groups of subjects: (i) 358 Kuwaiti Type 2 diabetics (156 men and 202 women) referred for their annual evaluation to the specialised diabetic clinic at the main university teaching hospital in Kuwait, and (ii) 47 healthy age and sex matched non-diabetic Kuwaiti control population (13 men and 34 women). Serum sialic acid levels were significantly higher (P<0.001) among the diabetic patients (mean+/-S.D.) (81.2+/-13.2 mg/dl) compared to the non-diabetic controls (66.9+/-11.0 mg/dl). Kuwaiti diabetic women had significantly higher concentrations compared to diabetic men (85.2+/-12.1 vs. 75.9+/-13.0 mg/dl, P<0.001). Among the controls there was no significant gender difference in sialic acid levels of women, (68.3+/-11.6 mg/dl) versus men (63.2+/-8.2 mg/dl). The gender difference in the diabetic patients was unrelated to the degree of obesity. Significant correlations were found between serum total sialic acid concentrations and such cardiovascular risk factors as plasma levels of apolipoprotein B, low density lipoprotein cholesterol, triglycerides and uric acid in the diabetic subjects. Furthermore, there was a significant elevation in serum total sialic acid concentrations with increasing urinary albumin excretion, P<0.001, but not with retinopathy or neuropathy.

We assessed the prevalence of coronary heart disease (CHD) risk factors including insulin resistance in 500 (205 males, 295 females) healthy elderly (age > 55 years) indigenous, low socioeconomic group Yorubas residents in either an urban slum (n = 240) or a rural town (n = 260) in southwestern Nigeria. Anthropometric indices, blood pressure and fasting plasma levels of glucose, lipids, insulin and insulin resistance were measured. The results indicated that: (i) gross obesity (4.4%), diabetes (1.6%), hyperlipidaemia (0.2%) and cigarette smoking (4.8%) were relatively uncommon in the population, although the prevalence of hypertension (30%) was higher than previously reported from this population; (ii). the subjects had a relatively high prevalence of multiple CHD risk factors (about 20% had > 4 risk factors), an observation considered paradoxical in view of the reportedly low CHD prevalence in this population; (iii) these CHD risk factors (increased body mass and blood pressure (BP), hyperinsulinaemia and insulin resistance) were more prevalent in the women and in urban residents; (iv) hyperinsulinaemia (20%) and insulin resistance (35%) were common in the population, and were associated, on regression analyses, to such other CHD risk factors as BP and body mass, particularly in women, suggesting, as in Caucasians, that insulin resistance could be an important index of CHD risk; and (v) the excess of multiple CHD risk factors in the women, is due at least in part, to their increased tendency to obesity (8%) and reduced physical activity (83%). This study concludes that: (i) despite the high prevalence of multiple risk factors in this population, CHD prevalence is low, indicating the supremacy of such major risk factors as diabetes and hyperlipidaemia (relatively uncommon here) in the development of CHD; and (ii) potentially the greatest CHD risk is in the elderly women especially if relatively overweight, physically inactive and resident in an urban centre. While further confirmatory studies are necessary in younger subjects and across societal socioeconomic strata, our results nonetheless suggest that attempts to maintain the CHD prevalence at low levels in this population should include efforts directed at reducing excess body weight particularly in women, and advice on maintenance of a traditional diet to keep lipid levels and diabetes prevalence low.

The aim was to establish whether risk factors for cardiovascular disease (CVD) are positively and independently associated with fasting insulin and/or body mass and waist-hip ratio in healthy elderly Nigerian subjects. Fasting plasma glucose, insulin, total cholesterol, triglycerides, blood pressure, and basal insulin resistance (HOMA method) were measured in 500 healthy elderly (> or = 55 years) Nigerian volunteers (295 men, 205 women). Associations between blood pressure, triglycerides or cholesterol and fasting insulin, HOMA, body mass index (BMI) or waist-hip ratio were examined using linear regression. Age was controlled for in all analyses. In men, diastolic and systolic blood pressure were strongly associated with BMI, while there was no evidence of an independent relationship with fasting insulin or HOMA. Triglycerides were strongly associated with waist-hip ratio, with a weaker independent association with HOMA but not fasting insulin; fasting insulin and HOMA showed strong independent associations with total cholesterol. In women diastolic and systolic blood pressure were also strongly associated with BMI, but there was an independent relationship with fasting insulin for diastolic blood pressure and a less significant (p = 0.057) one for systolic blood pressure. Triglycerides were significantly associated with BMI but none of the other variables; there were no significant associations with cholesterol. There was no evidence of interaction between fasting insulin or HOMA and BMI or waist-hip ratio. The results suggest the hypotheses that in this population BMI or waist-hip ratio are stronger determinants of blood pressure and triglyceride levels than fasting insulin or HOMA, and that where insulin does play a role its effects are separate and additive.