Plasma lipoprotein (a) levels in Turkish NIDDM patients with and without vascular diabetic complications.

OBJECTIVE: Plasma concentrations of lipoprotein (a) [Lp(a)], an independent risk factor for atherosclerosis, were measured in 59 non-insulin-dependent diabetes mellitus (NIDDM) patients with and without vascular complications, and 21 non-diabetic healthy subjects. RESULTS: The plasma log Lp(a) levels were found to be significantly increased in the NIDDM patients (1.40 +/- 0.36) compared with the healthy subjects (1.02 +/- 0.53; p < 0.05). Plasma Lp(a) levels in NIDDM patients with diabetic vascular complications (1.51 +/- 0.27) were significantly higher than those of the NIDDM patients without diabetic vascular complications (1.23 +/- 0.43) and healthy subjects (p < 0.05). There were significant correlations between plasma log Lp(a) levels and apolipoprotein B (apo B) in all NIDDM patients (r: 0.68, p < 0.05). No correlation was observed between Lp(a) levels and age, sex, duration of diabetes, fasting blood glucose, haemoglobin Alc, the mode of treatment, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein Al levels in all patients. CONCLUSIONS: It was concluded that Lp(a) was a risk factor for angiopathy in NIDDM patients and the patients who have a high plasma Lp(a) concentration should be kept under strict glycaemic control.     

Anthropometric studies in diabetes in the Tropics

Summary Anthropometric studies were carried out in three groups of diabetics seen in southern India, namely fibrocalculous pancreatic diabetes (FCPD) (n=49) (a subtype of malnutrition related diabetes), insulin dependent diabetes mellitus (IDDM) (n=55) and non-insulin dependent diabetes mellitus (NIDDM) (n=104). Both FCPD and IDDM had significantly lower body mass index, skinfold thickness (triceps, biceps, subscapular and suprailiac), mid-arm circumference and fat mass compared to controls and NIDDM patients, (p<0.001 for all parameters). FCPD and IDDM males did not show any significant differences in any of the anthropometric parameters studied. Among the females, FCPD had lower triceps skinfold measurements (p=0.007) and mid-arm circumferences (p<0.05) compared to IDDM patients. Patients with NIDDM did not show any significant difference compared to the control group. This study shows that both FCPD and IDDM patients have lower body mass and fat mass compared to NIDDM patients and control subjects.     

Lipoprotein(a) concentration is not associated with venous thromboembolism in a case control study.

BACKGROUND AND OBJECTIVE: Lipoprotein(a) is an LDL-like particle displaying strong athero-thrombotic properties. Although Lp(a) plays a pivotal role in the genesis and progression of thrombosis in the arterial district, its role in promoting thrombosis in the venous district is still unclear. DESIGN AND METHODS: To give further insight into the thrombotic potential of Lp(a), 100 potentially eligible consecutive outpatients who had suffered from previous episodes of venous thrombosis (deep vein thrombosis with or without pulmonary embolism) were enrolled into the study. Thirty-six of these patients who did not fulfil the entry criteria were then excluded from the study. The concentration of Lp(a) was thus measured in 64 patients, and compared to that of 64 control subjects, matched for sex (p=0.46), age (p=0.25) and pharmacological treatment; no subject belonging to the control group had a familial or personal history of venous thromboembolism. Exclusion criteria for both groups included: diabetes mellitus, liver or kidney diseases and malignancy, as established by both laboratory analysis and physical examination. To rule out false elevations of Lp(a) due to the presence of a concurrent acute phase response, C reactive protein (CRP) was measured in both groups using a commercial immunonephelometric assay. RESULTS: No statistically significant differences were observed in the median Lp(a) concentration between patients and controls (median: 69 vs 83 mg/L, respectively; p=0.34). Neither were any significant differences found between patients who had suffered from deep venous thrombosis with (n=18) or without (n=46) pulmonary embolism (median: 73 vs 69 mg/L, respectively; p=0. 83). The concentration of CRP did not differ significantly between cases and controls (median: 1.8 vs 2.3 g/L, respectively; p=0.37). INTERPRETATION AND CONCLUSIONS: Although there are several plausible biological mechanisms to explain the strong thrombogenicity of Lp(a) in vitro, we failed to demonstrate a convincing association between Lp(a) and thrombosis in the venous district. Besides the proven prothrombotic role of Lp(a) in some selected clinical settings, it is thus conceivable that the contribution of Lp(a) to genesis and progression of the venous thrombosis might be marginal or efficiently counterbalanced in vivo. The clinical usefulness of including the measurement of Lp(a) among the screening tests for thrombophilic patients, therefore, remains questionable.     

Left ventricular systolic function in middle-aged patients with diabetes mellitus

In cross-sectional studies of asymptomatic diabetic patients, multiple abnormalities in left ventricular (LV) function have been found. Long-term significance of these abnormalities is unknown because follow-up studies have not been previously performed. LV ejection fraction (EF) by radionuclide angiocardiography was examined in middle-aged control Subjects (n = 44), in patients with insulin-dependent (IDDM) (n = 32) and non-insulin-dependent (NIDDM) (n = 32) diabetes mellitus at baseline and after 4-year follow-up. At baseline, all study subjects were free from cardiovascular disease. LVEF at rest did not differ between the groups at baseline. The decrease in LVEF at rest during follow-up was 1.1 ± 1.1% (mean ± SEM) in control subjects, 3.1 ± 1.3% (p = NS, compared with control subjects) in patients with IDDM, and 7.2 ± 1.4% (p <0.01) in patients with NIDDM. At follow-up examination, abnormally low LVEF at rest (<50%) was found in 7% of control subjects, 13% of patients with IDDM (p = NS), and in 31% of patients with NIDDM (p <0.05). Compared with control subjects, the prevalence of an abnormal LVEF response to exercise (an increase by <5%, or a decrease) was higher in diabetic groups at both examinations. This prevalence increased in control subjects from 10% at baseline to 26% at follow-up examination. In patients with IDDM, the respective increase was from 43% to 52% (p = NS, compared With control subjects), and in patients with NIDDM from 53% to 73% (p = NS). Duration and metabolic control of diabetes, presence of diabetic complications, and LVEF at rest or during exercise at baseline did not differ in either diabetic group between the patients who had normal or abnormal LVEF at rest or in response to exercise at follow-up examination. No study subject experienced clinical heart failure during follow-up, but 7% of control subjects, 37% of patients (p <0.001) with IDDM, and 34% of patients (p <0.01) with NIDDM had coronary artery disease at follow-up examination. In conclusion, LVEF at rest deteriorated significantly during 4-year follow-up in patients with NIDDM but not in patients with IDDM. A high prevalence of subclinical LV systolic dysfunction became evident both in patients with IDDM and patients with NIDDM as an abnormal LVEF response to exercise both at baseline and follow-up examinations.     

Non-insulin-dependent diabetes and renal replacement therapy

Reports of renal replacement therapy in diabetes usually refer to patients with insulin-dependent diabetes mellitus (IDDM) only, and little is known about renal failure in non-insulin-dependent diabetics (NIDDM). A high proportion, 46/141 (32%), of the diabetics treated at our unit since 1974 had NIDDM. They were older at treatment (56 +/- 9 years, mean +/- SD) compared to the IDDM patients (39 +/- 10 years, p less than 0.001), and had a shorter duration of diabetes (13 +/- 8 years versus 23 +/- 8 years, p less than 0.001). Asians and Afro-Caribbeans accounted for 48% of the NIDDM patients (22/46) compared to only 7% of those having IDDM (6/95, p less than 0.0001). Non-diabetic renal disease accounted for the renal failure in 32% (15/46) of the NIDDM patients but only in 10.5% (10/95) of the IDDMs (p less than 0.001). Despite these differences the prevalence of other diabetic complications (retinopathy, neuropathy, and cardiovascular disease) was similar. Patient survival after transplantation was poorer in NIDDM than IDDM (23% and 57%, respectively, at 2 years). Survival on dialysis was equally poor in NIDDM and IDDM. Thus, NIDDM patients treated for renal failure are more commonly non-European and more often have non-diabetic renal disease. Yet other diabetic complications occur to the same extent in both IDDM and NIDDM patients with diabetic nephropathy.     

The frequency and severity of retinopathy are related to HbA1c values after, but not at, the diagnosis of NIDDM

OBJECTIVES: To examine the relationship between previous glycaemic exposure and prevalence of retinopathy 8 years after diagnosis of diabetes in 58 islet cell antibodies (ICA)-negative noninsulin-dependent diabetes mellitus (NIDDM) patients and in a group of 14 ICA-positive 'NIDDM' and insulin-dependent diabetes mellitus (IDDM) patients. DESIGN AND METHODS: The Wisconsin retinopathy scale was used to assess the retinopathy which was graded into mild, moderate and severe nonproliferative diabetic retinopathy (NPDR), or proliferative retinopathy (PDR). The frequency and severity of retinopathy was related to HbA1c levels at diagnosis, and 3 and 5 years later. RESULTS: Thirty of the 58 ICA-negative NIDDM patients (52%) but only 2 of the 14 ICA-positive 'NIDDM' or IDDM patients (14%) had mild-moderate-severe NPDR 8 years after diagnosis (P = 0.02). None had PDR. Retinopathy 8 years after diagnosis in NIDDM (= 58 ICA-negative patients) was correlated with the degree of glycaemic control (HbA1c levels) at 3 and 5 years after diagnosis, but not to HbA1c levels at diagnosis. The relative risk for a higher average HbA1c (per percentage) at 3 and 5 years was 1.56 for any retinopathy vs. no retinopathy (95% confidence interval 1.1-2.2; P = 0.01) and 1.68 for moderate to severe NPDR in comparison with no DR and mild NPDR (95% confidence interval 1.0-2.8; P = 0.04). CONCLUSIONS: Retinopathy after 8 years of diabetes in NIDDM patients was associated with impaired glycaemic control during previous years but not with glycaemic control at baseline. Good glycaemic control may prevent retinopathy in patients with NIDDM.     

Association of fibrinogen and lipoprotein(a) as a coronary heart disease risk factor in men (The Quebec Cardiovascular Study)

Fibrinogen has been prospectively found to correlate with coronary heart disease (CHD) but a similar association has not been well established for lipoprotein (a) (Lp(a)). Plasma lipids, Lp(a), and fibrinogen levels were measured in 2,125 men (aged 47 to 76 years) who were free of clinical CHD. During a 5-year follow-up period, 116 first CHD events were documented. Men with CHD were older, smoked more, had a higher prevalence of diabetes, and higher levels of systolic blood pressure, cholesterol, low-density lipoprotein cholesterol, Lp(a), and fibrinogen, and lower plasma high-density lipoprotein cholesterol levels. Only fibrinogen levels in the upper tertile of the distribution compared with the lower tertiles were associated with a significant risk of CHD (adjusted risk ratio 2.5; 95% confidence interval [CI] 1.4 to 4.2; p = 0.0010). Such an association was not observed with Lp(a). To assess a possible relation between fibrinogen and Lp(a) to the risk of CHD events, men were assigned to 1 of 4 groups according to fibrinogen median levels and a Lp(a) cut-off level of 300 mg/L: group 1: fibrinogen < 4.05 g/L and Lp(a) < 300 mg/L; group 2: fibrinogen < 4.05 g/L and Lp(a) > or =300 mg/L; group 3: fibrinogen > or =4.05 g/L and Lp(a) < 300 mg/L; and group 4: fibrinogen > or =4.05 g/L and Lp(a) > or =300 mg/L. Using group 1 as a reference, a significant risk ratio was only documented in group 4 (2.5; 95% CI 1.2 to 5.1; p = 0.0132). In this population, high fibrinogen levels associated with high Lp(a) levels significantly increased the risk of CHD.     

Correlation between serum lipoprotein (a) and angiographic coronary artery disease in non-insulin-dependent diabetes mellitus

Abstract. Comlekqi A, Biberoglu S, Kozan 0, Bahqeci 0, Ergene 0, Nazli C, Kinay 0, Guner G (Dokuz Eylul University, Medical School, Inciralti, Izmir, Turkey). Correlation between serum lipoprotein(a) and angio-graphic coronary artery disease in non-insulin-dependent diabetes mellitus. J Intern Med 1997; 242:449-54.
Objectives: To examine the impact of diabetic state on the concentrations of lipoprotein(a) [Lp(a)] in patients with non-insulin-dependent diabetes mellitus (NIDDM) and the correlation between angiographic coronary artery disease (CAD) and serum Lp(a) concentrations in NIDDM.
Design: In this cross-sectional study of 26 patients with NIDDM and 19 nondiabetic sex- and agematched patients who underwent coronary angiography, CAD was assessed visually using coronary artery score (CAS), and plasma Lp(a) was measured by an enzyme-linked immunosorbent assay.
Setting: The study was performed in an internal medicine clinic at a university hospital.
Subjects: Twenty-six age- and sex-matched patients with NIDDM and 19 control patients without diabetes.
Results: There was no significant difference between the Lp(a) concentrations of patientswith NIDDM and nondiabetic subjects (P > 0.05). When patients with NIDDM were stratified by absence or presence of CAD, patients with CAD had higher levels of Lp(a) (P < 0.05). However, there was no significant correlation between the concentrations of Lp(a) and CAS (P > 0.05).
Conclusions: Diabetic state does not have any impact on Lp(a) concentrations. Lp(a) excess seems to be atherogenic in patients with NIDDM as shown in nondiabetic patients in previous studies. Although diabetic patients with CAD have higher Lp(a) concentrations than the diabetic patients without CAD, Lp(a) levels were not correlated with CAS.     

The effect of long-term glycaemic control on serum lipoprotein(a) levels in patients with Type 2 diabetes mellitus.

AIMS: To examine whether long-term glycaemic control affects lipoprotein(a) (Lp(a)) levels in patients with Type 2 diabetes mellitus. METHODS: Eighty-nine Type 2 diabetic patients (38 men, 51 women) were recruited from the diabetes clinic. Based on HbA1c concentrations at baseline, patients were divided into two groups: those with HbA1c < 8.0% (n =45) and those with HbA1c > or = 8.0% (n=44). Comparisons of Lp(a) levels were made between both groups. The effect of long-term glycaemic control on Lp(a) levels was investigated in a subgroup of 20 patients, selected from those with baseline HbA1c > or = 8%. All these patients were treated with a goal of HbA1c <7%. RESULTS: Lp(a) levels were not significantly different between those with HbA1c< 8.0% and those with HbA1c, > or = 8.0%. No correlation between Lp(a) and HbA1c or fasting blood glucose levels was noted in diabetic patients as a whole. After 2 years of intensive glycaemic control, all patients exhibited remarkable improvement of therapy: their average HbA1c levels were 6.5 +/- 0.7%, being < 7% in 70% of patients. However, no change in Lp(a) levels were observed after 2 years (19.5 +/- 14.8-21.4 +/- 13.4 mg/dl, P = 0.390). CONCLUSION: These results indicate that improvement of glycaemic control does not affect serum Lp(a) levels in patients with Type 2 diabetes mellitus.     

Blood pressure changes in diabetes in urban Tanzania

Little is known of the natural history of blood pressure (BP) levels in diabetic patients from sub-Saharan Africa. BP levels were therefore recorded in such patients in Dar es Salaam, Tanzania, over 2, 5, and 7 years. Hypertension was found in 5% of insulin-treated diabetes mellitus (IDDM) and 29.2% of non-insulin-dependent diabetes mellitus (NIDDM) patients at presentation with diabetes. Hypertension developed in a further 2 IDDM (3.7%) and 27 NIDDM (15.6%) patients at 2 years, and in 3 IDDM (13.0%) and 9 NIDDM (9.8%) patients at 5 years. Seven NIDDM (18.4%) patients had developed hypertension by 7 years. In NIDDM patients with normal BP initially, the mean systolic BP rose from 131 to 141 mmHg (P<0.001) 2 years later (n=146); from 131 to 138 mmHg (P<0.001) for those followed for 5 years (n=82); and from 131 to 138 mmHg (P<0.05) for those followed for 7 years (n=31). The mean diastolic BP was 83 mmHg initially and 84 mmHg (NS) for those followed for 2 years (n=146). There was no observed rise in mean diastolic BP at 5 or 7 years of follow-up. In IDDM patients without hypertension, only the systolic BP rose significantly by 5 years, from 124 to 132 mmHg (P<0.001;n=20). These changes were independent of age, sex, body mass index, and proteinuria. We conclude that: (1) in black Tanzanians, as in other ethnic groups, it is likely that hypertension is significantly associated with diabetes; (2) rates of hypertension and BP levels continue to increase with time, particularly in NIDDM subjects; and (3) BP measurements should be a regular feature of diabetes care in the African diabetic population as in other populations.     

Presence of anti-DNA antibody in diabetes mellitus: its relation to the duration of diabetes and diabetic complications

In seven patients with insulin-dependent diabetes mellitus (IDDM) and 86 patients with non-insulin-dependent diabetes mellitus (NIDDM), serum anti-DNA antibody was measured by a semiquantitative radioimmunoassay (RIA) method. Prevalence of positive anti-DNA antibody (more than 20 U/mL) was five of seven in IDDM patients, 15 of 36 in NIDDM patients with insulin therapy, and seven of 50 in NIDDM patients without insulin therapy. None of normal subjects or patients with impaired glucose tolerance (IGT) showed positive anti-DNA antibody. The titer of anti-DNA antibody was higher in IDDM patients than in age-matched normal subjects (mean +/- SD; 22.1 +/- 15.3 v 6.5 +/- 2.2 U/mL, P less than .05). In patients with NIDDM, the antibody titer regardless of insulin treatment, was higher than in age-matched subjects with IGT (18.5 +/- 13.1 U/mL in NIDDM patients receiving insulin, 14.8 +/- 8.1 U/mL in NIDDM patients not receiving insulin, and 8.8 +/- 3.9 U/mL in IGT patients [P less than .001] for either of NIDDM groups v IGT). The titer of anti-DNA antibody was positively correlated with the duration of diabetes (r = .413, P less than .001) and with the postprandial blood glucose level (r = .311, P less than .01) in NIDDM patients when all of them were combined and analyzed as a group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of elevated lipoprotein(a) levels and coronary heart disease in NIDDM patients. Relationship with apolipoprotein(a) phenotypes

Summary Non-insulin-dependent diabetes mellitus (NIDDM) is a strong and independent risk factor for coronary heart disease. We assessed the potential relationship between plasma Lp(a) levels, apo(a) phenotypes and coronary heart disease in a population of NIDDM patients. Seventy-one patients with coronary heart disease, who previously have had transmural myocardial infarction, or significant stenosis on coronary angiography, or positive myocardial thallium scintigraphy, or in combination, were compared with 67 patients without coronary heart disease, who tested negatively upon either coronary angiography, myocardial thallium scintigraphy or a maximal exercise test. The prevalence of plasma Lp(a) levels elevated above the threshold for increased cardiovascular risk (>0.30 g/l) was significantly higher (p=0.005) in patients with coronary heart disease (33.8%) compared to the control group (13.4%). The relative risk (odds ratio) of coronary heart disease among patients with high Lp(a) concentrations was 3.1 (95% confidence interval, 1.31–7.34;p=0.01). The overall frequency distribution of apo(a) phenotypes differed significantly between the two groups (p=0.043). However, the frequency of apo(a) isoforms of low apparent molecular mass (700 kDa) was of borderline significance (p=0.067) between patients with or without coronary heart disease (29.6% and 16.4%, respectively). In this Caucasian population of NIDDM patients, elevated Lp(a) levels were associated with coronary heart disease, an association which was partially accounted for by the higher frequency of apo(a) isoforms of small size. In multivariate analyses, elevated levels of Lp(a) were independently associated with coronary heart disease (odds ratio 3.48, p=0.0233).Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - IDDM insulin-dependent diabetes mellitus - CHD coronary heart disease - Lp(a) lipoprotein(a) - apo(a) apolipoprotein(a) - apoB apolipoprotein B - HMGCoA reductase hydroxymethylglutaryl coenzyme A reductase     

Plasma glucose responses to glucose, sucrose, and honey in patients with diabetes mellitus: an analysis of glycaemic and peak incremental indices

We have studied the hyperglycaemic effect of the carbohydrate of glucose, sucrose, and honey equivalent to 20 g in twelve normal volunteers, eight patients with insulin-dependent diabetes mellitus (IDDM), and six patients with non-insulin-dependent diabetes mellitus (NIDDM). Honey produced an attenuated postprandial glycaemic response in normal volunteers (vs glucose p less than 0.005; vs sucrose p less than 0.05) and IDDMs (vs glucose p less than 0.005; vs sucrose p less than 0.05). The glycaemic index (GI) showed considerable variability within each subject group. Combined with a peak incremental index (PI), the two indices appear to be more valuable in predicting the glycaemic effects of carbohydrates rather than either one alone. We suggest that honey may prove to be a valuable sugar substitute in diabetics, and that both the GI and PI should be used in the analysis of food.     

Elevated levels of soluble E-selectin in patients with IDDM and NIDDM: relation to metabolic control

Summary The adhesion of leucocytes to the endothelium, an early step in atherogenesis, is mediated by cell adhesion molecules. In this study we evaluated the concentration of soluble adhesion molecules in patients with insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) and studied its relation to glycaemic control. Soluble adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were measured in 31 diabetic patients (18 with IDDM and 13 with NIDDM), 20 hyperlipoproteinaemic patients (10 with type IIa and 10 with type IIb) and 20 healthy subjects. Increased E-selectin concentrations were found in the patients with IDDM and NIDDM and in the hyperlipoproteinaemic patients when compared to the control subjects (p<0.01 for all the groups). ICAM-1 was found to be elevated only in the patients with NIDDM (p<0.01). No significant differences in VCAM-1 concentration were found in the different groups of subjects. The concentration of plasma E-selectin was positively correlated with the glycated haemoglobin (r=0.54, p<0.01) in patients with IDDM and NIDDM. In the same patients E-selectin was not related to the concentrations of plasma lipids in spite of the fact that it was found to be elevated in hyperlipoproteinaemic subjects. The results though preliminary suggest that in diabetic patients the concentration of soluble adhesion molecules and especially of E-selectin may be related to metabolic control.Abbreviations IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - ICAM-1 intercellular adhesion molecule-1 - VCAM-1 vascular adhesion molecule-1 - AGE advanced glycation end products     

Knowledge profile and control in diabetic patients

Knowledge about diabetes was assessed using a previously described interactive computer-based questionnaire in 79 patients with insulin-dependent (IDDM) and 72 with non-insulin-dependent (NIDDM) diabetes mellitus routinely attending a single diabetic clinic. Simple linear correlation of total knowledge score with glycosylated haemoglobin (HbA1c) showed no significant relationship for either IDDM (r = 0.12: p = 0.18) or NIDDM (r = 0.15: p = 0.1). However, quintile grouping of knowledge scores showed the mean HbA1c to be significantly higher in the lowest scoring NIDDM quintile (10.6 +/- 0.5: +/- SE) with respect to the pooled mean of all the higher scoring quintiles (9.0 +/- 0.3) (p = 0.027). Mean HbA1c (9.6 +/- 0.5) was also higher in the least knowledgeable IDDM quintile than any other quintile group (range 8.8-9.0) but this was not significant with respect to the pooled mean of higher scoring patients (p greater than 0.1). The mean age of the lowest scoring IDDM quintile group (60.5 +/- 13.9 years) was significantly higher (p less than 0.01) than higher scoring IDDM groups (mean age range 36.5-43.3 years) but age was not significantly related to HbA1c in IDDM subjects. IDDM showed greater knowledge of diabetes than NIDDM but ignorance in key areas was unacceptably high in both diabetic subtypes, indicating that regular knowledge assessment and educational reinforcement may be essential for good diabetic control as well as patient safety, particularly in older IDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diurnal variation of blood ketone bodies in insulin-dependent diabetes mellitus and noninsulin-dependent diabetes mellitus patients: the relationship to serum C-peptide immunoreactivity and free insulin

We examined whether the rise in ketone body concentration around midnight and in the early morning was due to the lack of free insulin (IRI) or excess of insulin counterregulatory hormones such as human growth hormone (hGH), cortisol and glucagon in noninsulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) patients and whether the monitoring of blood ketone body concentration was clinically useful as an index of metabolic control for deciding to increase or decrease the insulin dose in the treatment of diabetes mellitus. Serum levels of 3-hydroxybutyrate (3-OHBA), acetoacetate (AcAc) and 3-OHBA/AcAc ratio before breakfast were significantly increased in insulin-treated NIDDM patients with well-controlled fasting plasma glucose levels and IDDM patients compared to those in normal subjects. Mirror image diurnal changes were found between serum concentrations of 3-OHBA and serum C-peptide or free IRI in normal subjects and NIDDM patients treated with diet alone or sulfonylurea during the 24-hour daily profiles. However, there were no correlations between 3-OHBA and free IRI in the NIDDM patients treated with insulin and IDDM patients who had a much larger increase in the mean concentration of serum 3-OHBA at 6 a.m. caused by a low concentration of free IRI. Counterregulatory hormones were not increased in IDDM patients compared to normal subjects in the early morning. Cortisol/free IRI and hGH/free IRI molar ratios were significantly increased in NIDDM and IDDM patients compared to normal subjects in the early morning, but glucagon/free IRI molar ratio was not changed between IDDM and normal subjects. In conclusion, the early morning rising of ketone body concentration in insulin-treated diabetic patients, particularly IDDM patients, is due to the absolute lack of free IRI and/or the relative lack of free IRI to the levels of hGH or cortisol, and the monitoring of 3-OHBA is clinically useful as a more sensitive index of metabolic control.     

Lipoprotein(a), left atrial appendage function and thromboembolic risk in patients with chronic nonvalvular atrial fibrillation

Lipoprotein(a) (Lp(a)) has a prothrombotic effect by modulating the fibrinolytic system. The purpose of the present study was to determine whether serum Lp(a) levels are associated with an increased risk of thromboembolism in chronic nonvalvular atrial fibrillation (NVAF). Clinical, laboratory and transesophageal echocardiographic data were collected in 172 consecutive, non-anticoagulated patients with chronic NVAF. Thirty-four patients (thromboembolic group) had a recent (<1 month) embolic event and/or a left atrial thrombus on transesophageal echocardiography. The thromboembolic group had a higher frequency of spontaneous echo contrast (94 vs. 58%, p<0.0001), increased concentrations of Lp(a) (median: 31.5 vs. 15.5 mg/dl, p<0.0001) and fibrinogen (median: 352 vs. 314 mg/dl, p = 0.0015), larger left atrial dimensions (median: 5.1 vs. 4.8cm, p = 0.0078), and reduced left atrial appendage (LAA) flow velocities (median: 9.5 vs. 21.2 cm/s, p<0.0001) than the nonthromboembolic group. Multivariate analysis identified 3 independent predictors of thromboembolism: Lp(a) level > or =30 mg/dl (odds ratio (OR) 9.5, 95% confidence interval (CI) 4.4-20.4, p<0.0001), LAA flow velocity of <20 cm/s (OR 8.7, 95% CI 3.3-23.0, p = 0.0003) and a fibrinogen concentration of <377mg/dl (OR 3.2, 95% CI 1.5-6.9, p = 0.0201). The Lp(a) elevations and reduced LAA flow velocities are independently associated with thromboembolism in chronic NVAF.     

Prospective follow-up study of renal function in type 2 diabetes

Type 2 diabetes mellitus is the main cause of increase in patients suffering from end-stage renal failure in France. We performed an observational study of the change in renal function of type 2 diabetic patients, attending our diabetology clinic. Clinical and biological data were regularly entered in an informatic database (Pénélope, Poitiers University Hospital). We prospectively followed 351 type 2 diabetic patients (age at diagnosis: 40 to 75 years), for 32 months (extremes: 1-120). Renal function was graded in 4 stages according to plasma creatinine and urinary albumin excretion (UAE) determined by nephelometry on random urinary sample: absent (UAE < 20 mg/L et creatinine < 150 mumol/L), incipiens (UAE 20 to 200 mg/L and creatinine < 150 mumol/L), established (UAE = 200 mg/L et creatinine < 150 mumol/L) advanced (creatinine = 150 mumol/L). Glycated haemoglobin (HbA1c) was determined by HPLC. Systolic/Diastolic Blood Pressure (SBP/DBP) was measured with a mercury sphygmomanometer. We defined renal events as the change from one stage of nephropathy to a higher one. A total of 351 type 2 diabetic subjects were studied: 194 men/157 women mean age 63 +/- 11 years, mean diabetes duration 10 +/- 9 yr. At baseline, 206 patients had no nephropathy, 98 incipient nephropathy, 28 established nephropathy and 19-advanced nephropathy. Baseline stage of nephropathy was related to SBP (p < 0.0001), DBP (p = 0.0002), diabetes duration (p = 0.0064) but not HbA1c (p = 0.2182) or sex (p = 0.4794). Among those 332 subjects without baseline advanced nephropathy, 134 progressed in nephropathy. Progression of nephropathy was not related to the presence of hypertension (SBP/DBP > or = 160/95 mmHg) (log-rank = 0.22; p = 0.6377). Conversely, patients with a poor glycaemic control (HbA1c > or = 10%) had a worse renal-event free survival (log-rank = 4.89; p = 0.0269). Glycaemic control is a risk factor for the progression in nephropathy of type 2 diabetic patients.     

Plasma urate in diabetes: relationship to glycaemia, glucose disposal, microvascular complications and the variations following oral glucose.

In order to provide further insights into the conflicting reports of associations between diabetes and uric acid metabolism, we studied 175 adult diabetic patients (56 IDDM, 119 NIDDM) and 114 matched control subjects. Plasma uric acid (PUA) concentrations were not significantly different between diabetic and control subjects, despite increased urinary urate in diabetic patients. There were no significant associations, in diabetic patients, between PUA and (i) type of diabetes, (ii) glycaemic control, (iii) retinopathy and (iv) proteinuria. Plasma urate did not correlate with the KG constant for glucose disposal rate during IVGTT, thus indicating that PUA may not be related to insulin action. In a separate study, PUA rose sharply, peaking at 30 min, and fell subsequently in both newly diagnosed NIDDM patients (n = 20) and subjects with impaired glucose tolerance (n = 15) in response to standard OGTT, in contrast to normal controls (n = 35) in whom PUA rose gradually to a peak at 120 min. Mean rise in PUA from baseline to peak was significant (P less than 0.05) in the diabetic group only. These differences in PUA response during an OGTT between subjects with abnormal glucose metabolism and normal controls may be a feature in the metabolic evolution of diabetes and need further investigation.