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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.

There is an inverse correlation between plasma high density lipoprotein (HDL) concentrations and atherogenic vascular morbidity risk. An important pathway for modulating circulating HDL levels is the reaction catalysed by the plasma enzyme, lecithin:cholesterol acyltransferase (LCAT). Thus, determinants of LCAT activity should influence plasma HDL levels and be accessible targets for intervention. We therefore assessed such determinants in Nigerian patients with non-insulin dependent diabetes mellitus (NIDDM), classified into age- and sex-matched groups of obese (body mass index, BMI, > 25 kg/m2) and non-obese (BMI < 25 kg/m2). Our results indicated that 10 obese diabetic patients had significantly reduced plasma LCAT activity and HDL levels and increased plasma triglyceride (TG) levels, in comparison with the observations in 9 non-obese diabetic patients (all P < 0.05). Furthermore, worsening of glycaemic control, when oral hypoglycaemic treatment was discontinued for 1 week in 10 diabetic (5 obese) patients, further reduced fasting levels of HDL and plasma LCAT activity (both P < 0.05). Although plasma HDL concentrations and LCAT activity levels did not correlate significantly, the latter nonetheless had a significant inverse relationship with fasting plasma glucose levels in the obese diabetic subjects (r -0.51, P < 0.05). These results indicate that glycaemia and body mass are important determinants of plasma LCAT activity. Both variables are subject to pharmacological and dietary intervention with the objective of increasing circulating HDL levels.

Objective: To examine the phases of acute insulin release and glucose homeostasis in people of African descent with and without a positive family history of type II diabetes who reside in geographically diverse environments. The prevalence of type II diabetes in people of African descent varies considerably depending on the country of habitat. Family history is recognized as an important risk factor for the development of the disease., Research Design and Methods: We studied serum glucose and insulin concentrations--before and after intravenous glucose challenge--in glucose-tolerant, first-degree relatives of African-American (n = 18) and Nigerian (n = 20) type II diabetic patients and their respective healthy control subjects (African American, n = 9; Nigerian, n = 18) living in their native countries. The acute first- (t = 0-5 min) and second-phase (t = 10-60 min) insulin releases were calculated as the sum of incremental insulin responses to the intravenous glucose stimulation., Results: Mean serum glucose levels and glucose decay constant (KG) were not different in the African Americans and Nigerians. Fasting serum insulin in the African-American relatives was significantly greater than the Nigerian relatives (16.0 +/- 3.0 vs. 5.8 +/- 1.7 mU/L, P < 0.05). In contrast, FSI levels in the African-American control subjects were similar to Nigerian control subjects (6.3 +/- 1.4 vs. 4.5 +/- 1.8 mU/L). Acute first- and second-phase insulin levels were 2-3 times (P < 0.01) greater in African Americans than Nigerians, irrespective of family history of diabetes. Comparing the African-American relatives with healthy control subjects, we found significantly (P < 0.05) higher FSI in the relatives; whereas the acute first- (272 +/- 44 vs. 222 +/- 55 mU/L) and second-phase (388 +/- 61 vs. 235 +/- 53 mU/L) serum insulin release tended to be greater, but not significantly different in the relatives. In contrast, the acute first (101 +/- 15 vs. 120 +/- 20 mU/L) and second phase (88 +/- 14 vs. 111 +/- 17 mU/l) of insulin release were slightly lower, but not significantly different, in the Nigerian relatives versus the Nigerian healthy control subjects. In a subgroup of nonobese African-American (n = 11) and Nigerian (n = 11) relatives, and African-American (n = 8) and Nigerian (n = 7) healthy control subjects with a body mass index < 30 kg/m2, the mean fasting and post-stimulation serum glucose were not different. However, serum insulin concentrations in the African Americans were significantly different from those of the Nigerians. The pattern of insulin responses in the nonobese subjects was similar to those of the respective African-American and Nigerian groups., Conclusions: Our preliminary study demonstrates greater serum insulin responses and, perhaps, insulin resistance in glucose-tolerant African Americans than in their Nigerian counterparts, irrespective of family history of diabetes and obesity. We conclude that the antecedent lesions leading to the development of type II diabetes may be different in the first-degree relatives of African-American and Nigerian diabetic patients.

Objective: The aim of the study was to investigate changes in insulin sensitivity during the menstrual cycle, in a group of regularly menstruating black African women., Method: Insulin responses to intravenous glucose (300 mg/kg) were assessed, for up to 3 h, in 3 groups of age- and body mass-matched non-obese sedentary Nigerian women: Group A, 7 women in the menstrual follicular phase; Group B, 7 women in the menstrual luteal phase; C, 7 men., Result: Women in the menstrual luteal phase had the greatest integrated first-phase insulin response and insulin/glucose ratios, much higher than the similar values for these variables obtained in other groups. This suggests that the menstrual luteal phase is associated with relative insulin resistance., Conclusion: Black African women in the menstrual luteal phase demonstrate an exaggerated insulin response to an acute glucose load and are thus relatively insulin-insensitive. This confirms previous observations in Caucasians.

We analysed blood insulin and glucose concentrations before and during frequently sampled intravenous glucose tolerance tests (FSIGT) in 2 groups of Nigerian subjects: (A) Control group (n = 18), without a positive family history of diabetes mellitus, and (B) Experimental group (n = 16), comprising age-, sex- and body mass-matched first-degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM). In comparison with Group A subjects, those in Group B had: (i) higher fasting plasma glucose level (mean +/- S.E.M. 4.1 +/- 0.1 vs. 3.8 +/- 0.11 mmol/l, P < 0.05); (ii) similar fasting serum insulin levels (6.7 +/- 5.0 vs. 5.8 +/- 5.6 mU/l, P = NS); (iii) lower mean incremental area under the first-phase (t = 0-10 min) post-glucose challenge insulin curve (376.9 +/- 8.8 vs. 435.6 +/- 5.6 mU/min l-1, P < 0.05); (iv) increased incremental area under the second-phase (t = 10-182 min) post-glucose challenge insulin curve (432.9 +/- 11.5 vs. 161.3 +/- 8.7 mU/min l-1, P < 0.05); (v) reduced KG rate constant of glucose elimination (0.97 +/- 0.12 vs. 1.41 +/- 0.12%/min, P < 0.05). These results suggest that the subjects with a positive family history of NIDDM have a reduced beta-cell insulin secretory reserve (from reduced first-phase insulin response), tendency to rebound hyperinsulinemia during the latter phase of the insulin secretory response, a degree of tissue insulin insensitivity (as evident from high fasting plasma glucose despite similar insulin levels) and a diminished glucose disposal rate, in comparison with subjects without a family history of NIDDM. These features predict subsequent development of diabetes and suggest that as in Caucasians, first-degree relatives of Nigerian patients with NIDDM are at greater risk for future development of the disease.

In assessing the relationship between insulin levels and blood pressure, we analyzed glucose and insulin data after standard 75 g oral glucose tolerance tests in 16 nonobese male Nigerian subjects with essential hypertension and compared their results with those obtained from 16 age- and sex-matched healthy normotensive subjects. The fasting plasma glucose and insulin as well as 2-hour postload insulin values were similar in both groups. The hypertensive subjects had significantly greater 2-hour glucose levels, larger incremental areas under the glucose/time curves, and smaller ratios of incremental insulin to incremental glucose areas (P < .05). These parameters suggest some impairment of glucose tolerance in the hypertensive subjects related to an inadequate insulin response to the oral glucose load. Model analysis of the glucose and insulin data confirmed these observations in that the estimated rate of glucose uptake into peripheral tissues (M value) was lower in the hypertensive subjects (P = .02). There was no correlation at any time point between insulin values and blood pressure in either group of subjects. These results suggest that essential hypertension in Nigerian diabetic subjects is associated with a reduced insulin response to glucose loading, which is at variance with reports in whites, and deserve further investigation.

Intraperitoneal glucose tolerance tests were performed at 4-week intervals in groups of weanling rats before and after feeding with maize- or cassava-based diets with and without adequate protein and sublethal cyanide supplementation. Weaning weights were doubled (increase of about 50 g) after 4 weeks on control (maize-based with adequate protein) and protein-replete diets. Weight gain on the protein-deficient diets was much less (22 g or 50%), a pattern maintained by the rats on these diets until the age of 12 weeks. Plasma thiocyanate levels were identical at weaning and after 8 weeks of the control diet but increased by 200-300% after 4 weeks intake of the cassava or cyanide-supplemented feeds. Levels returned to normal in all groups after a further 4 weeks feeding with the control diet. Glucose tolerance (as assessed by the area under the 2 h glucose v. time curve) was impaired to a varying extent in the rats after 4 weeks on the various diets: protein-replete cassava and protein-deficient maize diets by 50% protein-deficient cassava diet by 300%, and cyanide-supplemented protein-deficient maize diet by 150%. The derangement in the rats on the protein-replete cassava diet was unaffected by a further 4 weeks intake of the control diet, unlike in the other groups where there was significant improvement in the glucose tolerance indices at the same time. It is concluded that in growing rats: (1) cassava intake and protein malnutrition may have independent and additive effects on the genesis of glucose intolerance, (2) cyanide supplementation of a cassava-free protein-replete diet has no effect on glucose tolerance.

Standard (75 g) oral glucose tolerance tests were performed at two different ambient temperatures (23 and 33 degrees C) in random order in 16 (eight obese) diabetic and 16 (eight obese) non-diabetic Nigerian subjects. Consistently higher plasma glucose values were found 120 min post-glucose ingestion at 33 degrees C, with mean differences of 0.5 (SE 0.3) and 4.5 (SE 1.5) mmol l-1 in the non-diabetic and diabetic subjects, respectively. This caused reclassification of two of the non-diabetic subjects as Impaired Glucose Tolerance at 33 degrees C, applying the WHO criteria. The difference was consistently greater (p less than 0.01) in the non-obese subjects (non-diabetic 0.8 (0.4), diabetic 6.9 (2.8) mmol l-1) than in the obese (non-diabetic 0.2 (0.4), diabetic 2.1 (0.9) mmol l-1). In the diabetic subjects, a negative correlation (r = -0.50, p less than 0.01) was established between the difference and the body mass index. This variability in responses to ambient temperature between the obese and non-obese subjects could be due to a variable influence of heat on arm blood flow consequent on differences in amounts of subcutaneous fat. The ambient temperature for the conduct of the oral glucose tolerance test is important.

There have been a few reports in Caucasians that glucose tolerance is worse at higher environmental temperatures. In investigating these observations in a tropical African population, we performed standard oral glucose tolerance tests in the morning after overnight fasting in 16 diabetic (with varying glycaemic control) and 16 nondiabetic subjects, both groups with differing body weights. Each volunteer ingested 75 g glucose at two different ambient temperatures of 22-23 degrees C and 32-33 degrees C in random order. These room temperatures are typically observed during hot and humid seasons in sub-Saharan Africa. Our results confirm that glucose tolerance was worse at the higher room temperature (p less than 0.01). The post-oral glucose 2 h values at the lower room temperature were lower by about 5 mmol/l in the diabetics and 0.5 mmol/l in the non-diabetics (both p less than 0.02). Similarly, the total and incremental areas under the 2 h glucose/time curves were greater at the higher room temperature. These results were not influenced by obesity. We conclude that glucose tolerance in tropical Africans is dependent on environmental temperature. An ambient temperature for the performance of diagnostic oral glucose tolerance test should therefore be specified, especially when evaluating differences in diabetes prevalence rates in populations resident in different climatic regions.

We examined changes in blood concentrations of glucose, acetate and other blood intermediary metabolites as well as the disposal of an intravenous glucose load during successive glucose-free acetate and control bicarbonate haemodialysis in random order, in non-diabetic and diabetic subjects. Plasma acetate levels increased about 10-fold in both the diabetic and non-diabetic subjects during the 1st hour of acetate dialysis. This was accompanied by about 5-fold increase in the levels of the ketone bodies-acetoacetate and 3-hydroxybutyrate. Ketone body levels did not change during bicarbonate dialysis. Additionally, the changes in blood levels of glucose, non-esterified fatty acids, pyruvate, lactate, glycerol and insulin were similar with either bicarbonate or acetate treatment in each subject group. The KG rate constant of glucose disposal after intravenous glucose (10 g/m2 body surface area) given after the 1st hour of a 5-hour haemodialysis was similarly unchanged with acetate or bicarbonate dialysis, despite the additional caloric load likely from the high blood levels of acetate obtained during acetate haemodialysis. We conclude that the major metabolic effect of acetate during haemodialysis is an increase in blood ketone body levels. Glucose utilisation, as assessed from the KG rate constant of glucose disposal or changes in blood lactate and pyruvate levels, was not affected by the high acetate levels attained during dialysis.

We measured cortisol levels in plasma and saliva samples obtained simultaneously from 10 fasting adult Nigerians at 0900 h and at 60 and 90 min of hypoglycaemia induced by intravenous insulin. Salivary glucose levels (fasting and after i.v. insulin) were unaffected by hypoglycaemia and did not correlate with plasma glucose at any time point. Cortisol levels in plasma and saliva increased by 50% and 120%, respectively, from fasting to 90 min values (both P less than 0.05) after i.v. insulin. This increase was evident by 60 min (plasma 33% and saliva 40%, both P less than 0.05 compared to fasting values). There was a significant positive correlation between the percentage increases in plasma and salivary cortisol (r = 0.65, P less than 0.05). Salivary cortisol was always (0900 h and during hypoglycaemic stress) 15-20% of total plasma cortisol, a percentage similar to the reported values on the contribution of free plasma cortisol to total plasma cortisol. We conclude that increases in plasma cortisol are reflected in saliva, and salivary cortisol could be estimated as an alternative to free plasma cortisol in the dynamic assessment of adrenocortical function in humans.

We measured plasma glucose and thiocyanate levels before and up to 4 h after feeding 11 overnight fasted healthy non-diabetic volunteers randomly on three occasions each with three locally consumed cassava meals: (i) gari as eba 50 g; (ii) lafun 50 g and (iii) parboiled cassava flakes 76 g. Each of these meals contained 175 kcal (0.7 MJ) and was consumed with a sauce to a total caloric value of 300 kcal (1.26 MJ). On the fourth visit, each volunteer consumed 75 g glucose. While the peak and 2-h glucose values were greatest with oral glucose (P less than 0.01), they were similar with the three cassava meals, although tended to be lowest with lafun. Similarly, areas (incremental and total) under the glucose/time curves were highest with oral glucose (P less than 0.05), but while eba and cassava flakes were similar, lafun had the lowest values (P less than 0.05). Plasma thiocyanate levels were unchanged after ingestion of oral glucose and eba, but increased to peak values (P less than 0.05) by 14 per cent on cassava flakes and by 23 per cent on lafun. We conclude that post-prandial glycaemia and plasma thiocyanate levels after cassava meals depend on the mode of preparation of the meal and that lafun showed the least glycaemic response of the three cassava meals tested although it caused the greatest increase in plasma thiocyanate levels. These findings suggest that a cyanogenetic potential does not always reflect a tendency to hyperglycaemia.

In investigating the interrelations of plasma acetate with glucose metabolism, we established that fasting plasma acetate levels (mmol/l) were greater in the diabetic than non-diabetic individuals (p less than 0.001). Plasma acetate and glucose levels correlated in all subjects (non-diabetic and diabetic) as a whole (rs 0.28, p less than 0.0001) and in the diabetics alone (rs 0.35, p less than 0.001). After i.v. glucose (20 g/m2 body surface area), plasma acetate levels increased further in the diabetic and non-diabetic individuals. Plasma acetate also increased when non-diabetic individuals consumed 75 g oral glucose. Moreover, while plasma acetate levels had returned to fasting values by 90 min in the non-diabetic subjects after oral and i.v. glucose, levels remained elevated in the diabetics after i.v. glucose. The K rate constant of glucose elimination after i.v. glucose in the diabetics correlated negatively with acetate values at many time points. In the non-diabetics, changing acetate and glucose levels after oral glucose also correlated at multiple time points. These results suggest that the plasma acetate level is influenced by variations in glycaemia and provide further evidence for an impaired rate of acetate metabolism in diabetes.

In attempting to resolve the existing controversy on the effect of dietary salt intake on glycaemic responses, we investigated post-prandial plasma glucose levels in 10 healthy normal weight non-diabetic Nigerian subjects (aged 23.1 years +/- 1.3 (s.e.m.) with body mass index, BMI 19.9 +/- 0.6 kg/m2) consuming equal amounts of carbohydrate from glucose, boiled yam (low fibre content of 0.9 per cent raw tuber weight) and boiled black-eyed peas (high fibre content of 4.8 per cent dry weight) with and without added table salt (4.25 g). The results indicated no significant differences in fasting, peak and 2-h plasma glucose concentrations and total and incremental areas under the 3-h glucose/time curves in the subjects consuming each meal with and without added salt. Added salt had no influence on the glycaemic index of each meal. We conclude that salt has no effect on the glycaemic response to plain glucose or meals with varying fibre content even in a population known to demonstrate defects in salt handling.

We measured plasma levels of acetate, glucose, insulin, fatty acids and 'ketone bodies' (KB), during fat infusion and continuous simultaneous infusion of insulin and glucose according to a computerized algorithm to maintain fasting euglycaemia and derive indices of tissue insulin sensitivity (hyperinsulinaemic euglycaemic clamping HEC). (i) Plasma acetate levels (mmol/l) approximately doubled (0.14 +/- (SEM) 0.02 to 0.25 +/- 0.02, p less than 0.01) during INTRALIPID infusion in 7 non-diabetic individuals while total 'ketone bodies' and non-esterified fatty acids (NEFAs) increased 10-fold. (ii) Early in the HEC, plasma acetate levels decreased as did NEFAs in 13 non-diabetic (0.17 +/- 0.01 to 0.12 +/- 0.01, p less than 0.001) and 9 diabetic (0.22 +/- 0.02 to 0.15 +/- 0.01, p less than 0.005) individuals. However while acetate levels later rose to fasting values in the non-diabetics, they remained low in the diabetics. NEFA levels were low throughout the clamp but glucose flux was increased as judged from the glucose infusion even with maintained euglycaemia. The change in acetate values during the second hour of the clamp correlated with neither BMI nor two indices of insulin sensitivity (glucose metabolic clearance rate and steady state glucose infusion rate). These results accord with acetate production from glucose and fat oxidation, via acetyl CoA. The differing metabolism of acetate in the second hour of clamping between diabetics and non-diabetics may reflect altered post-receptor glucose metabolism with the onset of diabetes.

When either a 960-kcal, 140-g carbohydrate meal, or a 75-g glucose load was ingested by non-diabetic Caucasians, the 2-h venous plasma glucose concentration was higher by 0.82 and 1.25 mmol/l, respectively, if the ambient temperature was 33 degrees C rather than 23 degrees C. It is likely that this is a result of relative 'arterialisation' of the venous blood. Even at 23 degrees C room temperature, use of the 'hot hand' technique to obtain 'arterialized' venous blood increases post-load glucose levels in contralateral antecubital veins. If these observations apply to those acclimatised to the heat, they could affect the diagnosis of both diabetes and impaired glucose tolerance in the tropics.