ABSTRACT
Epidemiological profile of non-insulin-dependent diabetes mellitus The incidence of non-insulin-dependent (i.e. type II) d iabetes m ellitus (NIDDM) is increasing markedly in adult urban populations around the world. In the early decades of the twenty-first century this disease is destined to become a major global public health problem: the approximately 3 per cent of adults currently affected will become an estim ated 5 per cent by 2025 [World H ealth Organization (WHO) 1998a] as populations ‘age’ and urbanise, and as obesity becomes more prevalent (WHO 1998b).Two striking epidemiological features of NIDDM are the wide variation in prevalence between populations, and, at the individual level, the strong positive corre la tion w ith relative body w eight. The m ore th an tenfold difference in NIDDM prevalence between Pim a Indians (of Arizona, U nited States) and Polynesians at the high extrem e, South Asian and West Africans in the middle range, and European populations at the low extrem e, could reflect population differences in genetic susceptibility, in exposure to environm ental factors, or both. The persistence of elevated rates of NIDDM in South Asian m igrants several generations after m igration to the U nited Kingdom suggests that genetic factors are im portant (McKeigue 1997a). On the other hand, the similar elevations in NIDDM prevalence rates in urbanised Indian, Chinese and African m igrant populations in M auritius testify to the im portance of environm ental (presum ably lifestyle) factors (Zimmet and Alberti 1997). So, too, does the approxim ately fivefold difference in NIDDM prevalence between rural and urban populations in Tamil Nadu, southern India, living a mere 20 miles apart (McKeigue 1997a).In adult individuals, body mass index (BMI) is very strongly correlated with im paired glucose tolerance (IGT) and with NIDDM, especially if the increased adiposity is centripetal (‘abdom inal’). Short-term studies of the covariation of weight and glucose tolerance confirm tha t this is a causal relationship (Sims et al. 1973, O ’Dea 1991). More recently, evidence from cohort studies in W estern populations has shown that the incidence of IGT
and of NIDDM is raised in individuals of low birth weight (particularly those with low ponderal index: i.e. low w eight/length ratio), especially if those individuals also become overweight in adulthood (McKeigue 1997b). This increased risk may reflect the long-term consequences of fetal metabolic adaptation (‘program m ing’) to an tenatal nutritional insufficiency (Barker1994). The role of insulin in diabetes NIDDM is a serious metabolic disorder that causes end-organ dam age to the kidneys, heart, blood vessels and retina. The disease process is the result of ‘insulin resistance’ - a reduction in the body’s sensitivity to insulin. This pancreatic horm one is central to the m etabolic production, storage and mobilisation of the body’s m ain fuels: glucose and free (non-esterified) fatty acids.Insulin secretion in to the blood is s tim u la ted by the post-prandial absorption of simple sugars (from carbohydrate), fatty acids (from fat) or amino acids (from protein). In persons of average BMI, insulin reduces blood glucose levels by replenishing liver stores of glycogen and by increasing the deposition of glucose as glycogen in muscle. Insulin also stim ulates the liver to convert fatty acids to low-density lipoprotein cholesterol and triglycerides, which are then released into the bloodstream and, under insulin action, stored in peripheral adipose tissue. Insulin, conversely, inhibits the mobilisation of glucose and fa tty acids from th ese s to rag e tissu es . M eanw hile , in circumstances of low intake of carbohydrate foods (as with Inuit Eskimos - see Van der Merwe 1992) excess dietary amino acids can be converted by the liver to glucose (by ‘gluconeogenesis’) or, in other circumstances, to lipids.These major actions of insulin are sum m arised in Figure 10.1. The figure indicates that, under normal conditions, the dom inant effect of insulin is to enhance the peripheral deposition of glucose and lipid as energy stores. Insulin has various other metabolic effects not shown here (including influencing urinary sodium and nitrogen excretion, sym pathetic nervous system tone and leptin sensitivity).The m echanism of im p airm en t of insulin action has not yet been determ ined. It may entail the down-regulation of either cell-surface insulin recep to r activity or in trace llu la r tran sp o rt of glucose, or some o th er m odulation (Clausen et al. 1995). Insulin sensitivity is also reduced by leptin, the hormone secreted by adipose tissue (Bray 1996). Hence, in obese persons, raised leptin levels achieve negative feedback by reducing insulin action and thus lim iting the further deposition of energy in fat cells (which may help explain the increase in insulin resistance associated with obesity). However, th is re la tio n sh ip was p resum ab ly not im p o rtan t in h u n te r -g a th e re r populations, in whom obesity was a rarity. Indeed, in the historically usual non-obese circumstance, leptin’s main role was probably in the hormonal triggering of ovulation in adequately nourished women.
