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We investigated the potential relationship between hyperhomocysteinemia and the presence of coronary heart disease (CHD) and chronic complications in a consecutive series of 358 (156 men) Kuwaiti type 2 diabetic subjects. The median (2.5(th), 97.5(th) percentiles) fasting plasma concentration of total homocysteine (tHcy) in the patients was 10.2 (5.4, 19.1) micromol/l. Fasting tHcy concentration was significantly (p<0.001) higher among men [11.3 (7.1, 24.6) micromol/l] compared to women [8.8 (5.3, 16.3) micromol/l]. Of the 57 patients with a history of CHD and/or electrocardiographic (ECG) evidence of CHD, 9 (16%) had hyperhomocysteinemia (tHcy > or =15 micromol/l) compared to 8.3% (25 of 301) of patients without evidence of CHD. In univariate analysis, plasma tHcy concentration was significantly (p<0.01) higher in those diabetic subjects with history of CHD and/or abnormal ECG. Although hyperhomocysteinemia was more common in patients with microalbuminuria (15%) compared to patients with normoalbuminuria (12%), there was no significant association between hyperhomocysteinemia and the degree of albuminuria. After controlling for age and sex, multiple regression analyses showed significant associations of plasma tHcy concentration with glycated hemoglobin (p<0.05), plasma concentrations of creatinine (p<0.001) and apolipoprotein-B (p<0.05), but not with smoking, neuropathy or retinopathy. It seems that the association of hyperhomocysteinemia with diabetic microvascular complications is mediated by the confounding effect of other factors like age, sex and plasma creatinine concentration. In conclusion, we have found a univariate association between hyperhomocysteinemia and CHD but not with microalbuminuria, neuropathy and retinopathy. Although routine estimation of plasma homocysteine may be useful, the association with cardiovascular disease or microvascular complications in patients with type 2 DM deserves prospective studies.

The assessment of markers of systemic inflammation, such as C-reactive protein (CRP) and interleukin 6 (IL6), could be used to identify persons at high risk of coronary heart disease (CHD). This study evaluates the relationship of CRP and IL6 with CHD risk factors in patients with type 2 diabetes mellitus (DM) with CHD and age and sex matched type 2 DM controls without CHD. CRP, IL-6, total plasma homocysteine (tHcy), lipoprotein (a) [Lp(a)] and sialic acid (SA) were determined in 55 type 2 diabetic patients with CHD and 51 age- and sex-matched type 2 diabetic controls without CHD. Multivariate and logistic regression analyses were used to relate these markers with CHD risk factors. CRP (P=0.02) and tHcy (P=0.03) were significantly higher in patients with CHD compared with the control group even after correction for age and sex. IL6, Lp(a), SA and lipid parameters were not significantly different between the two groups of patients. After adjustment for potential confounders, the odds ratio (OR) for elevated CRP was 2.00 (95% confidence interval [CI], 1.12-3.58) (P=0.02) but the OR for IL6 was 3.41 95% CI, 0.70-17.17 (P=0.14). Partial correlation analyses of CRP and IL6 with other variables showed significant correlation of CRP with tHcy, and SA in patients with CHD only. Our results support the inclusion of CRP (high-sensitivity assay), in the risk assessment of diabetic subjects.

About 15% of the adult Kuwaiti population has type 2 diabetes and over 50% are hyperlipidaemic by current diagnostic criteria. Not surprisingly, coronary heart disease (CHD) is the leading cause of death in Kuwait. Reports from coronary care units in Kuwait suggest that 40-80% of the CHD patients were diabetic and 50-80% hyperlipidaemic. The pattern worldwide is similar. International guidelines have therefore consistently recognised diabetes as a major risk factor for CHD. In our Lipid Clinic population in Kuwait, about 30% are diabetic. The commonest lipid abnormalities seen in Kuwaiti diabetic patients, as elsewhere, are hypertriglyceridaemia with low HDL levels and variable LDL levels. About 75% of the subjects had either mixed hyperlipidaemia or predominant hypertriglyceridaemia. There are possibly some compositional changes in LDL in the diabetic subjects in that there were important differences in the statistical relationships between LDL and HDL and their respective apolipoproteins - apo B and apo A-1 in diabetic as compared to non-diabetic subjects. Other important observations made in diabetic subjects in Kuwait are: (i) similar serum Lp (a) levels and pattern of apo(a) polymorphism with non-diabetic subjects, with no demonstrable relationship between serum levels of Lp(a) and insulin/insulin sensitivity, although with CHD, Lp(a) levels were increased; (ii) diabetic hyperlipidaemic subjects had elevated PAI-1 levels with significant correlations between blood PAI-1 and insulin levels suggesting underlying insulin resistance (syndrome X). Various landmark trials of cholesterol-lowering therapies in the prevention of CHD have consistently demonstrated near-normalization of the increased CHD risk in diabetes. Our experience in Kuwait suggests that diabetic patients and others with mixed hyperlipidaemia benefit from tight glycaemic control, appropriate advice on diet and exercise with regular reinforcement by continuing contact with professional dietitians and regular availability of drugs where prescribed. Often, it is the regular compliance with medication that is important, rather than the specific medication used particularly where HMG CoA reductase inhibitors (statin drugs) are not always available. A useful guideline for management of dyslipidaemia in diabetes is suggested., (Copyright 2002 S. Karger AG, Basel)

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.

The aim of this study was to assess parameters of renal function and other determinants of plasma homocysteine in type 2 diabetic patients without coronary heart disease (CHD). Fasting plasma homocysteine, serum cystatin C and serum creatinine were determined in 183 (75 men, 108 women) Type 2 diabetic patients without clinical evidence of CHD. Creatinine clearance was calculated and parameters such as blood pressure, body mass index (BMI), and glycated haemoglobin (HbA(1c)) were assessed. The urine albumin:creatinine ratio was used to classify patients as normo-, micro- or macroalbuminuric. One hundred and ten patients were normoalbuminuric, 67 patients were microalbuminuric and six patients were macroalbuminuric. There was no statistically significant difference in plasma homocysteine concentration between patients with normoalbuminuria and microalbuminuria. There was a trend towards increasing plasma homocysteine with decreasing glomerular filtration rate (GFR) (r=-0.46; P<0.0001). There was statistically significant correlation between plasma homocysteine and age (r=0.37), serum cystatin C (r=0.47), and serum creatinine (r=0.56). Plasma homocysteine concentration was significantly higher in patients with BMI<30 kg/m(2) and showed significant inverse correlation with weight (r=-0.16; P=0.03) and body mass index (r=-0.24; P=0.001). Homocysteine and serum creatinine were significantly higher in males than females and higher in smokers than non smokers but was not associated with glycemic control and duration of diabetes. In conclusion, elevated homocysteine concentration in patients with type 2 DM without CHD is related to age, gender, smoking, BMI and GFR. Follow up studies will provide further information on the association between hyperhomocysteinemia and the development of cardiovascular disease.

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.

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.

Blood levels of intermediary metabolites were measured and indirect calorimetry was performed in 10 otherwise healthy, non-insulin-dependent diabetic (NIDDM) patients before, during, and after 30 minutes of moderate exercise on three occasions in random order at weekly intervals with (1) heparin treatment to increase preexercise plasma nonesterified fatty acid (NEFA) levels (HEPARIN); (2) acipimox, a nicotinic acid analogue, to reduce preexercise plasma NEFA levels (ACIPIMOX); and (3) no manipulation of preexercise plasma NEFA levels (NIL). With ACIPIMOX, preexercise blood levels were significantly reduced for NEFAs and glycerol (P < .01) and marginally reduced for acetoacetate and 3-hydroxybutyrate (NS) compared with preexercise levels for the other two treatments; these low levels seen with acipimox treatment increased only slightly during exercise and the postexercise period. Plasma NEFA levels increased by approximately 150% (P < .001) with HEPARIN at the same times. The levels of ketone bodies during either NIL or HEPARIN increased rapidly postexercise by approximately 90% to 110% for both acetoacetate and 3-hydroxybutyrate (both P < .01). Plasma insulin levels tended to be lowest (despite similar plasma glucose levels during the three treatments) with ACIPIMOX, while growth hormone (hGH) and, perhaps, noradrenaline levels were highest both during and after exercise. The respiratory quotient (RQ) was highest with ACIPIMOX (P < .05 for exercise and postexercise periods compared with the other two treatments), which, compared with NIL, reduced fat oxidation by 27% and 60% and increased carbohydrate oxidation by 29% and 74% during and after exercise, respectively (all P < .05). These changes in substrate oxidation due to ACIPIMOX were almost opposite to those observed with HEPARIN.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficiency of clearance of plasma triacylglycerols (TAG) after fatty meals in non-diabetic Caucasian subjects is believed to determine the plasma level of high-density-lipoproteins-cholesterol (HDL-C). It is unknown if this observation holds in diabetic subjects and in other racial groups. In assessing the factors that determine TAG responses to acute fat loading in a tropical African population with a low prevalence of atherosclerotic disease, twenty (nine obese) non-insulin-dependent diabetic (NIDDM) patients with optimal glycaemic control and twelve (six obese) age-matched non-diabetic subjects were given meals containing 50 g fat (in butter) and 75 g carbohydrate (in white bread) over 15 min in the morning after a 12 h overnight fast. The fasting plasma levels of glucose, TAG, total cholesterol (total-C), HDL-C, low-density-lipoprotein-cholesterol, insulin and glycosylated haemoglobin (HBAlc) were estimated; glucose and TAG levels were also measured postprandially for 8 h at 2 h intervals. Postprandial lipaemia was consistently higher in the diabetic patients (about 50-100% more than values obtained in the non-diabetic subjects, even when corrected for differences in body mass) and correlated positively with age and postprandial glycaemia. This defect in TAG clearance was even worse (by about 50%) when glucose tolerance became further impaired after ten of the diabetic patients stopped oral hypoglycaemic treatment for 1 week and the fat-tolerance test was repeated. In the obese non-diabetic subjects, but not those of normal weight, there were significant negative relationships between the postprandial lipaemia and fasting plasma levels of HDL-C and HDL-C: total-C ratio, as reported in Caucasians. It is concluded that age and the ambient glucose concentration appear to be the important determinants of the efficiency of TAG clearance in diabetic subjects. This accords with clinical observations of increased atherogenic liability with increasing age and poorer glycaemic control. The determinants in non-diabetic subjects were less defined, indicating that postprandial lipaemia might be influenced by various factors (obesity as shown here) in different subsets of individuals.

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.

It has been suggested that raised post-ethanol plasma acetaldehyde levels, from inhibition of aldehyde dehydrogenase, underlie the liability to chlorpropamide, alcohol flushing (CPAF). We tested the hypothesis that acetate formation from acetaldehyde, the reaction catalysed by that enzyme, was also likely to be affected by chlorpropamide (CP) medication. In six healthy non-diabetic 'non-flushers', fasting acetate (Ac +/- s.d. mmol/l) was 0.22 +/- 0.12, and increased by 0.47 +/- 0.14 to peak levels by 30 min after intake of 40 ml dry sherry, which increased plasma ethanol (mmol/l) levels to 10.2 +/- 6.0. After 5 days of CP (250 mg daily), fasting Ac (0.17 +/- 0.05) and increase to peak of Ac and ethanol after 40 ml sherry (0.56 +/- 0.12 and 8.9 +/- 7.2 respectively), were not changed (P n.s.). There was no correlation between Ac and ethanol at any time point. When the studies were repeated in five non-insulin-dependent diabetic 'flushers', both on regular CP medication and after 3 days without CP, there was again no significant difference in fasting and post-ethanol Ac levels between the two studies (fasting 0.18 +/- 0.04 v. 0.17 +/- 0.02, and increase to peak 0.62 +/- 0.13 v. 0.72 +/- 0.18, P n.s.). These results indicate that the conversion of ethanol to acetate is unaffected by CP medication, and furthermore that post-ethanol acetate levels do not predict liability to CPAF.

We investigated acetate utilization in humans by randomly intravenously infusing acetate (2.5 mmol/min) or bicarbonate (2.8 mmol/min) over 60 min into nine nondiabetic and six non-insulin-dependent diabetic subjects followed with or without bolus intravenous glucose (20 g/m2 body surface area). The acetate metabolic clearance rate (MCR) was greater in the nondiabetic subjects (50.4 +/- 14.9 vs 25.0 +/- 6.5 mL.min-1.kg-1, p less than 0.01) as were acetate elimination rate constant (Kac) (0.031 +/- 0.003 vs 0.026 +/- 0.004/min, p less than 0.01) and basal turnover rate (8.56 +/- 3.65 vs 4.92 +/- 1.03 mumol.min-1.kg-1, p less than 0.01); acetate half-time was thus shorter in the nondiabetics (22.6 +/- 2.2 vs 27.2 +/- 3.8 min, p less than 0.01). Kac was reduced and half-time was prolonged in all the subjects (p less than 0.001) when glucose was available. Prior acetate or bicarbonate infusion had no influence on either the KG rate constant of glucose elimination or the postglucose insulin responses in both subject groups. These results suggest that the infused acetate did not worsen glucose tolerance, glucose impaired acetate utilization unlike reported in ruminants, and acetate is rapidly metabolized in humans although at a slower rate in diabetics.

Haemoglobin A1 (HbA1) levels were measured in forty-five diabetic Nigerians and thirteen non-diabetic controls using disposable microcolumn kits based on affinity chromatography. The effect on HbA1 results of storage of whole blood samples for 1 week at room temperature and in a refrigerator was also evaluated. The mean +/- s.d. of HbA1 levels in diabetic patients and controls were 12.1 +/- 5.6% and 5.2 +/- 0.90% respectively. The difference was highly significant, P less than 0.001. Newly diagnosed diabetic patients who had not been on any treatment had significantly higher mean value of HbA1, 14.4 +/- 5.0%, than old patients already on treatment, 9.5 +/- 2.9%, P less than 0.01. In a group of nine patients, the mean +/- s.d. of baseline HbA1 value was 10.3 +/- 4.2% and after 1 week storage of different portions of the samples at room temperature and in a refrigerator, the mean +/- s.d. respectively were 9.8 +/- 3.6% and 11.0 +/- 4.2%. There was thus a slight decrease on storage at room temperature and a slight increase during refrigeration but the observed differences were not statistically significant. It is concluded that the glyc-affinity micro-column chromatography is a satisfactory and potentially useful method for measuring HbA1 levels in tropical developing countries. The method was easy to use and the assays could be run under average ambient room temperature without recourse to use of an air-conditioned room or a special chromatography chamber.

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.

Sodium acetate was infused intravenously at 2.5 mmoles/min for 60 min into 6 normal subjects and 6 non-insulin dependent diabetic patients. In control experiments the same subjects received equimolar sodium bicarbonate infusions. Plasma non-esterified fatty acid and blood glycerol levels fell during acetate infusion in both groups, suggesting impairment of lipolysis. The respiratory quotient fell on acetate infusion as expected, although total energy expenditure was unaffected. If acetate oxidation was assumed to be 90 per cent of the infusion rate, then it accounted for about 40 per cent of total oxygen consumption; fat oxidation was reduced, whilst carbohydrate oxidation was unchanged. These results suggest that resting energy expenditure is maintained during acetate infusion since acetate replaces fat as an oxidative fuel, without affecting glucose oxidation. The reduction in fat oxidation appears to be due to reduced fat mobilization from adipose tissue. The metabolic effects of acetate infusion are similar in normal and in non-insulin dependent diabetic subjects.

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.

Plasma lipid profiles--total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, triglycerides and phospholipids--were studied in relation to two parameters of diabetic control (fasting blood sugar (FBS) for short-term control and glycosylated haemoglobin (HBA1C) for long-term control) in 46 diabetic patients (22 insulin-dependent (IDDM) and 24 non-insulin dependent (NIDDM] and 22 non-diabetic control subjects. We confirmed the positive correlation between FBS and HBA1C. All diabetic patients had significantly higher triglyceride levels (P less than 0.05) than controls, which were not influenced by degree of glycaemic control. NIDDM patients tended to have higher than normal TC levels (P less than 0.05). In IDDM, TC level was positively correlated with HBA1C (r = 0.37, P less than 0.05), and negative correlations were established between FBS and HDL-cholesterol (r = -0.46, P less than 0.02) and the HDL-cholesterol:TC ratio (r = -0.49, P less than 0.01), suggesting an increased atherogenic risk with poorer diabetic control. It is concluded that lipoprotein abnormalities exist in Nigerian diabetics, though not as consistently as in Caucasians. The differences may be due to, among other factors, differences in genetic make-up, diet (typical African diet being rich in plant fibre and poor in cholesterogenic nutrients) and aetiology of the diabetic state (tropical diabetes being highly heterogeneous and now thought to be linked to malnutrition).

When 10 diabetic (five insulin-dependent) subjects with reasonable glycemic control were randomized from their usual (U) diet (about 30 g fiber/day) between two different but isocaloric high fiber diets, each sequentially over 6 wk [HF (55 g fiber/day) and HFS (55 g fiber/day with sucrose taken as 15 g three times daily, with meals)], plasma acetate (mmol/L) increased by 35% on both high fiber diets from 0.21 +/- 0.06 (SD) to 0.28 +/- 0.10 (HF) and 0.30 +/- 0.10 (HFS) (both p less than 0.01). This was higher than the random weekly variation in plasma acetate levels of 11% in six other glycemically stable diabetic patients. When the acetate value was expressed as acetate/glucose, i.e., relative to the fasting glucose level (since fasting levels of acetate and glucose consistently positively correlate), the increase was about 80%. Fasting plasma non-esterified fatty acid (NEFA) levels fell during the high fiber diets and correlated negatively with the fasting acetate level (rs -0.51, p less than 0.005). The fall in NEFA and rise in acetate levels appeared greatest with the sucrose-supplemented meals. These results suggest increased exogenous contribution to the plasma acetate level from increased colonic fermentation of dietary fiber and raise the possibility of using such measurements in the assessment of compliance to high fiber diets. The fall in NEFA levels associated with raised plasma acetate levels may contribute to the beneficial effects on glycemic control observed with the high fiber diets.

Although ischaemic vascular disease is uncommon in Nigerians (diabetic and nondiabetic), foot gangrene of vascular origin still causes considerable morbidity in Nigerian diabetics. One known cause of vascular disease is lipid abnormalities. We therefore measured plasma lipid levels in diabetic patients with foot gangrene of vascular origin and compared those results with values in diabetics without gangrene and nondiabetic subjects, in relation to other variables such as glycaemic control, disease duration and body mass index. 45 noninsulin dependent diabetics (10 with foot gangrene) and 22 nondiabetic control subjects were studied. Those diabetics with gangrene had poorer (p less than 0.001) short-term glycaemic control (as assessed from fasting blood glucose levels) than those without, although longer-term control (HBA1C) was similar in both groups. Plasma triglyceride levels were significantly elevated in diabetics with or without gangrene (p less than 0.001) compared to nondiabetic subjects, while total cholesterol levels were high only in those with gangrene (p less than 0.02) who also had a longer disease duration. Plasma phospholipid and HDL-cholesterol did not differ significantly from control values. We therefore conclude that the raised plasma cholesterol and longer duration of diabetes in those diabetics with foot gangrene may have contributed to the genesis of vascular disease in those subjects.