Subgroup Of Diabetic Patients Research Articles

Mental well‐being in people with non‐insulin‐dependent diabetes

We assessed the prevalence of minor mental disorder and depression in elderly patients with non-insulin-dependent (Type 2) diabetes mellitus as compared with control subjects and evaluated the associates of impaired mental well-being in diabetic patients. The study consists of a community-based group of patients (n = 82) with a 10 years' known duration of disease and nondiabetic control subjects (n = 115). In addition to clinical and laboratory examinations, self-rating questionnaires assessing minor mental disorder (General Health Questionnaire, GHQ) and depression (Zung Self-rating Depression scale) were completed by the patients and control subjects. The mean scores of GHQ and Zung scores tended to be higher in diabetic than in control subjects, but the frequency of case subjects was not different between the diabetic (GHQ: 40%; Zung: 11%) and nondiabetic groups (GHQ: 36%; Zung: 7%). These findings were explained by more severe symptoms in diabetic case subjects as compared to nondiabetic case-subjects. From the various parameters studied, the presence of symptomatic neuropathy was most strongly associated with depression and minor mental disorder in diabetic subjects. The results suggest that the impact of Type 2 diabetes per se on minor mental disorder or depression in elderly subjects is not overwhelming. However, a subgroup of diabetic patients seems to have markedly impaired mental well-being, and the treatment of its underlying factors may improve overall treatment compliance.

1013-109 Effect of Picotamide in Preventing Cardiovascular Events in 438 Diabetic Patients: Results of a Multi-Centre, Placebo Controlled, 18-Month Study

In the A.D.E.P (Atherosclerotic Disease Evolution by Picotamide) study 2,304 patients with peripheral obstructive arterial disease (POAD) were recruited for a double blind 18-month multi-centre trial comparing picotamide (300 mg t.i.d.), an antiplatelet drug which inhibits thromboxane A2 (TxA2) synthase and antagonizes TxA2 receptor, and placebo. In the study population as a whole, 151 events (13.1%) occurred on placebo and 122 (10.6%) on picotamide, with a relative risk reduction of 19%, (p = 0.056, Logrank test, intention to treat analysis). The effect of picotamide was assessed in the A.D.E.P subgroup of diabetic patients, in order to test if the drug was still effective in patients at higher risk of cardiovascular complications. Diabetic patients were 438 (230 on picotamide and 208 on placebo). Most of them were male (80%), with a mean age of 64 years (min 40, max 75). Six per cent were insulin-dependent. The main risk factors (smoking, hypertension, previous vascular surgery, ankle/arm pressure ratio, WBC count and fibrinogen) were similarly distributed in the two groups. Diabetic POAD patients on placebo suffered from a total of 33 cardiovascular events (12 major and 21 minor) (15.9%), whereas those on picotamide suffered from a total of 20 events (6 major and 14 minor) (8.7%) (relative reduction of risk: 45.2%, p = 0.022 at Logrank test, intention to treat analysis). Both major and minor events occurred more frequently in the placebo than in the picotamide group. The overall incidence of major events was 5.8% on placebo and 2.6% on picotamide (relative risk reduction of 59.8%). Death occurred in 6 patients on placebo (2.9%) and in 3 on picotamide (1.3%). Non fatal major events (stroke, myocardial infarction and amputation) were 6 on placebo and 3 on picotamide. Minor events were 10.1% on placebo and 6.1% on picotamide (relative risk reduction of 39.8%). Adverse reaction, mainly gastrointestinal, occurred in 16% of patients, regardless of the treatment. In conclusion, this analysis indicates that Picotamide significantly reduces cardiovascular events in diabetic POAD patients, suggesting its potential use in patients at high risk of atherosclerotic progression.

Teaching materials for structured patient education programmes for type II diabetic patients with and without insulin treatment

The aim of this study was to describe the epidemiology of self-monitoring of blood glucose and to identify specific characteristics of those subgroups of diabetic patients treated with insulin that are most likely to monitor their blood glucose according to medical recommendations. Data were collected on 1384 insulin-treated patients, enrolled from 35 diabetic outpatient clinics and 49 general practitioners' offices between December 1993 and June 1994. Seventeen Italian regions out of 20 were included in the study. Our data show that 418 (31%) diabetic patients treated with insulin had never practised blood glucose self-monitoring. In addition, only 242 patients (18.2%) self-monitored their glycemia with a mean frequency of at least once a day (29.7% among insulin-dependent diabetes mellitus (IDDM) and 13.9% among insulin-treated non-insulin-dependent diabetes mellitus (NIDDM-IT) patients). Patients' characteristics associated with a higher probability of practising blood glucose self-monitoring were age below 50 years, being treated at a diabetic outpatient clinic, hypertension, need of three or more insulin injections per day, history of hypoglycemic episodes, ability to self-manage insulin doses. Our study calls for vigorous efforts aimed at promoting the incorporation of clearly-defined educational programs at each level of care, in order to improve the motivation and self-care of diabetic patients. Furthermore, studies are necessary to identify subgroups of diabetic patients that truly need to self-monitor blood glycemia, and to assess the efficacy of the practice of self-monitoring of blood glucose in improving metabolic control and reducing acute and long-term diabetic complications.

Progressive Decline in Renal Function in Diabetic Patients With and Without Albuminuria

This study describes patterns of progression of albuminuria and renal function in a subgroup of 40 patients from a total cohort of 211 diabetic patients (118 type I, 93 type II) followed over a period of 8-14 years. Forty patients (18 with type I diabetes, 22 with type II diabetes) showed progressive increases in albumin excretion rate (AER) and/or decreases in creatinine clearance (CC) during the study period. Of these, AER alone increased in 15 patients, AER increased and CC decreased in 13 patients, and CC alone decreased in 12 patients, with a similar distribution of type I and type II diabetic patients in each group. Of the 28 patients who showed an increase in albuminuria, AER increased at an annual rate of 30-40%, resulting in a 4- to 8-fold increase in AER to > 20 micrograms/min during the study. Of the 25 patients who showed a decrease in renal function, CC decreased at an annual rate of 4-5 ml/min, resulting in an approximate halving of CC to < 90 ml/min during the study. The rate of fall in CC was not related to the presence or absence of concomitant increases in albuminuria. However, a significant preponderance of women in the group showed a decline in CC alone. The decline in CC was associated with an increase in plasma creatinine as well as a progressive decrease in urinary creatinine excretion, but the underlying mechanisms remain unexplained. These data support the concept that a subgroup of diabetic patients may show a decline in renal function in the absence of significant increases in AER.(ABSTRACT TRUNCATED AT 250 WORDS)

Current therapeutic management of diabetic nephropathy.

Roughly 40% of all patients with insulin-dependent diabetes mellitus (IDDM) develop diabetic nephropathy with proteinuria, hypertension and a decrease in glomerular filtration rate 10 to 20 years after the onset of the disease, and 5 years later most patients suffer from end-stage renal disease. Microalbuminuria, defined as an urinary albumin excretion rate (UAER) between 30 and 300 mg/day, strongly predicts the development of nephropathy in IDDM. Nearly all patients with IDDM, a decreasing glomerular filtration rate and a UAER > 300 mg/day have coexisting hypertensive disease additionally worsening renal function. We review the results of recent long-term studies of the current therapeutic management in diabetic patients by means of better blood pressure control, low-protein diet and near-normal blood glucose control in the early microalbuminuric phase as well as in the later phases of the disease characterized by diabetic nephropathy with a UAER > 300 mg/day. Since the large majority of studies have been performed on IDDM, our conclusions with regard to therapy are only valid in this subgroup of diabetic patients.

The Extracellular Matrix in Diabetic Nephropathy

In the subgroup of diabetic patients who are destined to develop the full spectrum of the clinical syndrome of diabetic nephropathy, the kidney is afflicted with a series of distinct structural lesions principally involving the extracellular matrices. Diabetic nephropathy is characterized by hypertrophy of both glomerular and tubular elements, progressive accumulation of extracellular matrix components in the glomerular mesangium, and thickening of the glomerular and tubular basement membranes. Albeit less well recognized, progressive tubulointerstitial fibrosis is also a feature of the syndrome. Irrespective of pathogenetic mechanisms (be they metabolic, hemodynamic, or genetic), the structural changes involving the renal extracellular matrix compartments are believed to be the basis for the appearance of overt dysfunction, namely, proteinuria, hypertension, and renal failure. Therefore, a full understanding of the mechanisms that culminate in irreversible kidney failure requires a closer inspection of the status of the extracellular matrix in diabetes. This review outlines the different structural changes that typically occur during the course of the disease. Both glomerular and tubulointerstitial changes are reviewed. Valuable structural-functional correlations have been derived from examining kidney specimens obtained from patients with a wide spectrum of disease stages. Experimental animal models, supplanted with recent investigations in tissue culture on the effect of high ambient glucose levels, have increased our understanding of the cellular mechanisms that underlie the disordered matrix composition. Alterations in the metabolism of the collagens, proteoglycans, and other matrix constituents are reviewed.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian blood pressure variation in diabetic patients with autonomic neuropathy.

To elucidate distinctive patterns of circadian variation of blood pressure in diabetic patients. Circadian variations and indices of blood pressure variability were examined by non-invasive ambulatory blood pressure monitoring. The indices were assessed for a correlation with various possible signs of autonomic neuropathy, including the coefficient of variation of the RR interval and orthostatic hypotension. The study was conducted on 38 normotensive diabetics and 15 age- and sex-matched non-diabetic controls, all of whom were outpatients at the Third Department of Internal Medicine in Nagoya University Hospital. Ambulatory blood pressure measurements were taken in all subjects and the coefficients of variation in the RR interval and postural changes in blood pressure were determined. The diabetic patients demonstrated a different pattern of circadian variation in blood pressure from that of the non-diabetics. Diurnal-nocturnal differences were significantly smaller in diabetics than in non-diabetic controls. Statistically significant correlations were found between diurnal-nocturnal differences in blood pressure and the duration of diabetes, glycaemic control, the coefficient of variation in the RR interval and the change in blood pressure on standing. A subgroup of diabetic patients with severe autonomic neuropathy showed the lowest diurnal-nocturnal differences. In diabetic patients with autonomic neuropathy circadian variations in blood pressure are blunted. Ambulatory blood pressure monitoring can detect these abnormal variations and therefore may be useful in evaluating diabetic autonomic neuropathy.

Normal tissue plasminogen activator and plasminogen activator inhibitor activity in plasma from patients with type 1 diabetes mellitus.

The fibrinolytic system was investigated in 38 patients (21 males and 17 females) affected by type 1 diabetes mellitus (18 free from complications, 10 with retinopathy, and 10 with autonomic neuropathy) and in 8 healthy controls. Two separate fibrinolysis-stimulating tests were done: standardized venous occlusion and 1-desamino-8-D-arginine vasopressin infusion. Plasma tissue plasminogen activator antigen and activity and plasma plasminogen activator inhibitor activity were measured. All the patients were in good metabolic control (mean HbA1c 7.4%, range 6.1-8.0%). No significant differences were observed either between the diabetic patients and the control subjects, nor among the subgroups of diabetic patients. The fibrinolytic system is probably not involved in type 1 diabetes mellitus.

Relation of skin capillary pressure in patients with insulin-dependent diabetes mellitus to complications and metabolic control.

Microvascular disease is a major problem in patients with diabetes mellitus. It has been suggested that diabetic microangiopathy may result from an increase in capillary blood flow and capillary hypertension, but direct evidence of capillary hypertension in such patients is lacking. We measured capillary pressure at the summit of the capillary loop by direct microcannulation of skin nail-fold capillaries and a dynamic method of pressure measurement in 29 patients with insulin-dependent (Type I) diabetes and 29 normal subjects matched for age and sex. Among the diabetic patients, 7 had had diabetes for less than one year, 12 had incipient nephropathy (albumin excretion, 20 to 200 micrograms per minute), and 10 had overt nephropathy (albumin excretion, greater than 200 micrograms per minute). In addition, seven patients with no evidence of nephropathy were studied before and after three months of improved glycemic control. The median capillary pressure in the diabetic patients was 20.4 mm Hg (range, 13.6 to 25.3), as compared with 16.7 mm Hg (range, 12.8 to 22.8; P less than 0.001) in the normal subjects. The values were higher in each subgroup of diabetic patients than in the corresponding group of normal subjects, but the values did not differ among the three subgroups of diabetic patients. In the seven patients who were studied before and after three months of improved glycemic control, the median capillary pressure fell from 20.0 mm Hg (range, 18.5 to 21.7) to 17.8 mm Hg (range, 14.1 to 20.3; P = 0.02). Nail-fold capillary hypertension may develop early in the course of diabetes, before the emergence of microvascular disease, and may be influenced by changes in metabolic control.

Antihypertensive efficacy and safety of perindopril in mild-to-moderate essential hypertension: Results of a double-blind multicenter study versus atenolol

A 3-month double-blind multicenter trial compared the efficacy and safety of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor, with atenolol in mild-to-moderate essential hypertension. A total of 190 patients, 49 of whom were diabetic, entered the perindopril-atenolol comparison. Of these, 163 had been previously treated and had a 4-week runin period on placebo; 27 had previously been untreated and received placebo for 2 weeks. At entry, all patients who had a supine diastolic blood pressure (DBP) of 95–115 mm Hg were randomized to receive perindopril 2 mg or atenolol 25 mg, once daily. Patients were assessed at 2 weekly intervals for the first month and then monthly for 2 more months. If supine DBP was >90 mm Hg, treatment was increased by stepwise doubling of dose up to 8 mg perindopril or 100 mg atenolol once daily, and later by the addition of hydrochlorothiazide 25 mg, (indapamide 2.5 mg in diabetic patients) once daily. The two groups were homogeneous prior to treatment except for supine and erect heart rate, which were higher in the perindopril group than in the atenolol group (p <0.05). Mean supine DBP was 101.1 ± 0.6 mm Hg in the perindopril group (n = 94) and 99.9 ± 0.6 mm Hg in the atenolol group (n = 96). After 3 months' active treatment, 74% of patients in the perindopril group achieved a supine DBP of ≤90 mm Hg and 73% of patients in the atenolol group achieved the same goal. Monotherapy controlled supine DBP in 67% of the perindopril group and 63% of the atenolol group. The decrease in supine DBP was not significantly different between the two groups (−12.9 ± 0.9 versus −14.7 ± 0.9 mm Hg) but the decrease in erect DBP was lower in the perindopril group (−10.3 ± 0.9 versus −13.4 ± 1.0 mm Hg, p <0.02). Heart rate was reduced in the atenolol group (p <0.001). Sixteen patients withdrew from the study; nine were attributed to adverse events, two in the perindopril group and seven, including one death, in the atenolol group. Cough was spontaneously reported by 13% patients of the perindopril group and 1% patients of the atenolol group. In 5% of the perindopril cases this was mild and associated with upper respiratory tract infection. The nature and incidence of other symptoms were similar with both drugs. Changes in laboratory parameters were minor and not significantly different between the two groups. Analysis of the subgroup of diabetic patients showed similar efficacy and safety results.

Silent ischaemia in diabetic men with autonomic neuropathy.

Autonomic neuropathy is associated with an increased incidence of silent myocardial infarction and sudden death. The purpose of this study was to investigate the prevalence of silent myocardial ischaemia in diabetic patients with autonomic neuropathy and without. Five standard autonomic function tests were performed on 41 men with diabetes: postural change in blood pressure, postural change in heart rate, heart rate response to deep breathing, heart rate response to Valsalva's manoeuvre, and blood pressure response to sustained handgrip. There were 17 patients with autonomic neuropathy (group A) and 24 with normal autonomic function (group B). All patients underwent 24 hour ambulatory electrocardiographic monitoring to detect silent ischaemia. There was no significant difference in risk factors for coronary artery disease or history of angina pectoris between these groups. The prevalence of silent ischaemia was 64.7% in group A (95% confidence interval (95% CI) 38.33 to 85.79%) and 4.1% in group B (95% CI 0.11 to 21.12%). This represents a relative risk of 42.2 (95% CI 4.5 to 39.4, p less than 0.001). These results are consistent with the concept that autonomic neuropathy may prevent the development of anginal pain and thus obscure the presence of ischaemic heart disease. Twenty four hour ambulatory electrocardiographic monitoring may identify a subgroup of diabetic patients with autonomic neuropathy who have myocardial ischaemia and to whom treatment may be offered.

Insulin-Dependent Diabetes Mellitus and Hypertension

Contrasting results have been reported regarding the prevalence of hypertension in insulin-dependent diabetes mellitus (IDDM), showing a slightly higher or normal percentage of IDDM patients with elevated blood pressure levels than in the general population. Most of the cross-sectional and prospective studies on the prevalence of hypertension in IDDM show an association between microalbuminuria and elevated blood pressure levels. However, it is not clear whether hypertension is simply secondary to kidney damage or whether hypertension occurs with or even before the development of impaired kidney function. Patients with IDDM have a higher exchangeable body Na+ pool. Na+ retention in IDDM is accounted for by several metabolic and hormonal abnormalities such as hyperglycemia, hyperketonemia, hyperinsulinemia, altered secretion, and resistance to atrial natriuretic peptide. High blood pressure appears to be dependent, at least at some phase, on expansion of extracellular fluid volume as a consequence of defects in the renal secretion of Na+ and water. On the other hand, a tendency toward Na+ retention characterizes all patients with IDDM, whereas hypertension develops only in a subgroup of diabetic patients. One possible explanation for these findings is that a genetic predisposition plays a role in creating susceptibility to hypertension and perhaps to diabetic nephropathy independent of diabetes, even if Na+ retention can further deteriorate this susceptibility to hypertension. With regard to this issue, it has recently been suggested that the risk of kidney disease in patients with IDDM is associated with a genetic predisposition to hypertension. Furthermore, diabetic nephropathy occurs in familial clusters, because diabetic siblings of nephropathic diabetic patients show a higher frequency of diabetic nephropathy than the diabetic siblings of nonnephropathic diabetic patients. One of the possible genetic markers that could be useful to identify the diabetic patients with susceptibility to hypertension and diabetic nephropathy is the Na+(-)Li+ countertransport activity in erythrocytes.

Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus

The reactive vascular-injuring amino acid homocysteine was measured in plasma samples from 79 well-characterized type 1 diabetic patients and 46 control subjects. Patients with proliferative retinopathy had higher homocysteine levels (15.0 +/- 6.3 mumols l-1; mean +/- SD, p less than 0.001; n = 42) than those with progressive retinopathy during a two-year period (10.4 +/- 1.6 mumols l-1; n = 12), no or minimal retinopathy (10.7 +/- 4.3 mumols l-1; n = 25), and the control subjects (11.0 +/- 3.4 mumols l-1). Within the group of patients with proliferative retinopathy increased homocysteine levels were confined to those patients that had serum creatinine levels greater than 115 mumols l-1 and/or an albumin:creatinine clearance ratio greater than or equal to 0.02 x 10(-3) (17.0 +/- 5.9 mumols l-1; n = 23), whereas those with no or only minimal nephropathy had levels (12.1 +/- 5.5 mumols l-1; n = 18) that were not different from the control group. We conclude that neither type 1 diabetes mellitus nor diabetic retinopathy per se is associated with increased plasma homocysteine levels. In contrast, homocysteine accumulates, probably owing to reduced glomerular filtration, in diabetic patients with advanced nephropathy. This suggests that homocysteine might contribute to the accelerated development of macroangiopathy seen especially in this subgroup of diabetic patients.

Serum Levels of Tumor Necrosis Factor and IL-1α and IL-1β in Diabetic Patients

Objective To determine whether chronic hyperglycemia causes increased levels of serum tumor necrosis factor (TNF) and interleukin 1 α (IL-1 α) and IL-1 β. Research Design and Methods Sera were obtained from 59 diabetic patients, 44 chronically ill nondiabetic patients, and 34 age-matched healthy control subjects. Mononuclear cells were isolated from a subgroup of diabetic patients and healthy control subjects. Results Except for a modest increase in the prevalence of detectable serum TNF levels in diabetic patients, the serum cytokines measured in this study did not appear to be altered in diabetes. In vitro TNF production by mononuclear cells was not altered in diabetic patients. However, in vitro IL-1 β secretion, in response to lipopolysaccharides, was reduced. Conclusions Diabetes mellitus is not associated with significant changes in serum levels of TNF, IL-1 α, or IL-1 β. In vitro secretion of IL-1 β in response to lipopolysaccharides may be reduced in diabetes.

Psychological stress and blood glucose regulation in Type I diabetic patients.

Fifteen Type I diabetic patients self-monitored daily mean blood glucose levels (BGL), psychological stress, diet, exercise, and insulin injections for a period of 8 weeks. Separate multiple-regression analyses were conducted for each subject to assess the predictability of BGL from stress reports, independent of the effects of diet, exercise, and insulin self-administration. Considerable individual variability in findings was evident, with stress predicting BGL in a statistically significant manner in 7 of the 15 subjects. Stress had a significant effect on BGL independent of diet, exercise, and insulin administration for each of these 7 subjects. Discussion focused on the problems of measuring the key self-management behaviors influencing BGL and on the possibility that a subgroup of diabetic patients may be BGL stress responders.

Hypercholesterolaemic effect of fish oil in insulin-dependent diabetic patients.

The effect of the daily administration of Max EPA fish oil (equivalent to 2.7 g per day of eicosapentaenoic acid) on serum lipid levels was examined in insulin-dependent male diabetic patients with cholesterol levels of less than 6.5 mmol/L. After three weeks of fish-oil supplementation there was a significant rise in total cholesterol levels, which was due largely to increases in low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)- cholesterol levels. The increase in HDL-cholesterol levels was accounted for by its HDL2 subclass. There was a decrease in serum triglyceride levels, but this was also observed in a control group of diabetic patients who did not receive fish oil and is probably explained by weight loss in this group. Similar changes in lipid levels were found in a subgroup of diabetic patients with retinopathy. The possible detrimental effect of the increase in total cholesterol and LDL-cholesterol levels after Max EPA fish oil at this dose may be offset by the selective rise in the protective HDL2 subclass.

Clinical Identification of Nondiabetic Renal Disease in Diabetic Patients with Type I and Type II Disease Presenting with Renal Dysfunction

A retrospective study was done on 109 diabetic patients who had renal biopsies during 1974-1984 to determine factors identifying nondiabetic renal disease in patients with diabetes mellitus presenting with renal dysfunction. Six of 49 (12%) patients with type I and 17 of 60 (28%) with type II diabetes mellitus had other renal diseases, with or without diabetic glomerulosclerosis. Multivariate predictors of other renal disease in type I diabetes mellitus were duration less than 5 years (p less than 0.001), absence of proteinuria (p less than 0.001), and absence of neuropathy (p less than 0.05). In type II diabetes mellitus these were late age of onset (p less than 0.001), absence of neuropathy (p less than 0.05), and Caucasian race (p less than 0.005). Some patients with other diseases appeared to respond to therapy directed at their nondiabetic glomerulosclerosis disease. We emphasize the need to distinguish between the subgroup of diabetic patients with nondiabetic renal disease from the majority who have diabetic glomerulosclerosis alone. The latter group should be spared the discomforts, risks, and costs of a renal biopsy.

Thyroid autoimmunity in type 2 (non-insulin-dependent) diabetic patients of Caucasoid, black and Mexican origin.

Four hundred and forty-nine patients with Type 2 (non-insulin-dependent) diabetes mellitus and 270 control subjects from Caucasoid, Mexican and black origins were screened for the presence of thyroid microsomal antibodies. Mexican female control subjects had a significantly higher frequency of thyroid microsomal antibodies when compared with black female controls (21% versus 6%, p less than 0.01). Type 2 diabetic patients did not have a higher frequency of thyroid microsomal antibodies when compared with their sex- and race-matched control counterparts. The subgroup of diabetic patients who required insulin for the control of their blood glucose did not have a higher frequency of thyroid microsomal antibodies when compared with non-insulin-requiring diabetic patients. In conclusion autoimmunity against thyroid gland, as manifested by thyroid microsomal antibodies, is not more common in Type 2 diabetic patients when compared with sex- and race-matched control subjects.

Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus.

To differentiate peripheral and hepatic insulin resistance in hyperinsulinaemic overweight Type 2 (non-insulin-dependent) diabetic patients (n = 17; 143 +/- 4% ideal body weight; mean +/- SEM) arterial concentrations and splanchnic exchange of glucose, pyruvate, lactate, non-esterified fatty acids, beta-hydroxybutyrate and acetoacetate, as well as the insulin production rate, were determined before and during oral glucose loads of 25 g or 100 g. Insulin production rate, hepatic insulin retention and splanchnic exchange of glucose and metabolites were estimated by means of the hepatic venous catheter technique. In the basal state insulin production rate was greater in overweight Type 2 diabetic patients (2.57 +/- 0.28 pmol.kg-1. min-1) than in healthy control subjects (1.68 +/- 0.17 pmol.kg-1.min-1; p less than 0.01). After ingestion of 25 g glucose, the cumulative insulin production rate exceeded normal values (p less than 0.05), but was below normal with 100 g glucose (p less than 0.01). Relative insulin trapping by the splanchnic bed in the diabetic patients was 54 +/- 3%, not different from normal. Following a 100 g glucose load, splanchnic insulin retention fell by 20% in the patients, and less consistently so in healthy controls. Splanchnic glucose output was normal in the diabetic patients both in the basal state and after glucose ingestion although the induced arterial blood glucose levels were greater in the diabetic patients than in control subjects (p less than 0.005). Splanchnic output of pyruvate (p less than 0.025), lactate (p less than 0.01), and beta-hydroxybutyrate (p less than 0.005) were greater in the basal state in the diabetic patients than in healthy subjects. However, no difference in splanchnic exchange was seen between the two groups in their metabolites' respective response to glucose ingestion. These data suggest that obese hyperinsulinaemic Type 2 diabetic patients may represent a subgroup of diabetic patients with predominantly peripheral, but compensated hepatic, insulin resistance being associated with an increased basal insulin production rate which only exhausts after ingestion of a large glucose load.