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OBJECTIVE--Chronic low-grade inflammation is a feature of obesity and is postulated to be causal in the development of insulin resistance and type 2 diabetes. The aim of this study was to assess whether overfeeding induces peripheral insulin resistance in lean and overweight humans, and, if so, whether it is associated with increased systemic and adipose tissue inflammation. RESEARCH DESIGN AND METHODS--Thirty-six healthy individuals undertook 28 days of overfeeding by + 1,250 kcal/day (45% fat). Weight, body composition, insulin sensitivity (hyperinsulinemic-euglycemic clamp), serum and gene expression of inflammation markers, immune cell activation, fat cell size, macrophage and T-cell numbers in abdominal subcutaneous adipose tissue (flow cytometry and immunohistochemistry) were assessed at baseline and after 28 days. RESULTS--Subjects gained 2.7 ± 1.6 kg (P < 0.001) and increased fat mass by 1.1 ± 1.6% (P < 0.001). Insulin sensitivity decreased by 11% from 54.6 ± 18.7 to 48.9 ± 15.7 µmol/(kg of FFM)/min (P = 0.01). There was a significant increase in circulating C-reactive protein (P = 0.002) and monocyte chemoattractant protein-1 (P = 0.01), but no change in interleukin-6 and intercellular adhesion molecule-1. There were no changes in fat cell size, the number of adipose tissue macrophages or T-cells, or inflammatory gene expression and no change in circulating immune cell number or expression of their surface activation markers after overfeeding. CONCLUSIONS--Weight gain-induced insulin resistance was observed in the absence of a significant inflammatory state, suggesting that inflammation in subcutaneous adipose tissue occurs subsequent to peripheral insulin resistance in humans. Diabetes 59:2164-2170, 2010, Chronic low-level inflammation may be a pivotal link between obesity, insulin resistance, and type 2 diabetes (1). Studies performed in mouse models of obesity and in humans have shown increases [...]

Individuals with insulin resistance and type 2 diabetes have an impaired ability to switch appropriately between carbohydrate and fatty acid oxidation. However, whether this is a cause or consequence of insulin resistance is unclear, and the mechanism(s) involved in this response is not completely elucidated. Whole-body fat oxidation and transcriptional regulation of genes involved in lipid metabolism in skeletal muscle were measured after a prolonged fast and after consumption of either high-fat (76%) or high-carbohydrate (76%) meals in individuals with no family history of type 2 diabetes (control, n = 8) and in age- and fatness-matched individuals with a strong family history of type 2 diabetes (n = 9). Vastus lateralis muscle biopsies were performed before and 3 h after each meal. Insulin sensitivity and fasting measures of fat oxidation were not different between groups. However, subjects with a family history of type 2 diabetes had an impaired ability to increase fatty acid oxidation in response to the high-fat meal (P < 0.05). This was related to impaired activation of genes involved in lipid metabolism, including those for peroxisome proliferator-activated receptor coactivator-1α (PGC1α) and fatty acid translocase (FAT)/CD36 (P < 0.05). Of interest, adiponectin receptor-1 expression decreased 23% after the high-fat meal in both groups, but it was not changed after the high-carbohydrate meal. In conclusion, an impaired ability to increase fatty acid oxidation precedes the development of insulin resistance in genetically susceptible individuals. PGC1α and FAT/CD36 are likely candidates in mediating this response., Relatives of individuals with type 2 diabetes are an ideal human model to test for mechanisms in the early development of insulin resistance because approximately two-thirds eventually develop diabetes, and [...]

OBJECTIVE--Inflammatory markers such as C-reactive protein (CRP) are associated with insulin resistance, adiposity, and type 2 diabetes. Whether inflammation causes insulin resistance or is an epiphenomenon of obesity remains unresolved. [...]

OBJECTIVE--To investigate 1) associations between environmental factors (alcohol consumption, hormone replacement therapy [HRT], and physical activity) and insulin resistance and secretion, independent of genetic influences; 2) the contribution of abdominal [...]

OBJECTIVE -- To investigate the reproducibility of the plasma glucose (PG) response to exercise in subjects with type 1 diabetes on a nonintensive insulin regimen. RESEARCH DESIGN AND METHODS -- [...]

Diabetic lower-limb problems are common for people with diabetes, with amputations 15% times more likely than in those without the condition. Recommendations from the Australian Diabetes Society for reducing diabetic lower limb disease are presented.

OBJECTIVE--To examine the effects of hormone replacement therapy (HRT) on lipid metabolism, glycemic control, total body and central abdominal fat, blood pressure (BP), and arterial pulse wave velocity (APWV) in [...]

Insulin resistance appears to be central to Obesity, NIDDM, hyperlipidemia, and cardiovascular disease. While obese women with abdominal (android) fat distribution are more insulin resistant than those with peripheral (gynecoid) [...]

Objectives--To identify patients with discrepantly high clinic blood glucose concentrations compared with self reported values and to assess whether such patients have errors in self monitoring technique. To determine whether, [...]

A retrospective audit of management of type 1 and type 2 diabetes mellitus reviewed the outpatient management of glycaemia, blood pressure and serum lipids in a Sydney teaching hospital and to assess whether current treatment targets were being met. Results revealed that a large number of patients were not achieving recommended treatment targets despite evidence that intensive control of cardiovascular risk factors reduces morbidity and mortality in type 1 and type 2 diabetes, thus necessitating investigation of current means to achieve treatment targets.

An explanation of how, historically insulin resistance brought together facets of metabolic syndrome and pathogenesis of diabetes and atheroma, which in the due course of time were overtaken by central obesity currently accepted as the core component of metabolic syndrome is presented. It is argued that the measurement of serum insulin levels to diagnose insulin resistance, though a valuable research tool, has no place in current clinical practice.

To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow‐up plans. Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 – 31 December 2012; outcomes follow‐up to 31 March 2016. Patients aged 18 years or more admitted to hospital from EDs. Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA1c) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more. New diagnoses of diabetes and documented follow‐up plans for patients with admission blood glucose levels of 14 mmol/L or more. Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow‐up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26%; adjusted odds ratio [aOR], 0.83; 95% CI0.42–1.7; P= 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31%; control, 86/278, 31%; aOR, 1.51; 95% CI, 0.83–2.80; P= 0.18). 30‐day re‐admission (31% v22%; aOR, 1.34; 95% CI, 0.86–2.09; P= 0.21) and post‐hospital mortality rates (24% v22%; aOR, 1.07; 95% CI, 0.74–1.55; P= 0.72) were also similar for patients in intervention and control hospitals. Glucose and HbA1cscreening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed. Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.

Background: The increasing prevalence of obesity has focused attention on the contribution of physical activity and its interaction with predisposing genetic factors. Objective: To examine 1) the relation between physical activity and total-body and central abdominal fat, independent of genetic and other environmental factors, and 2) the influence of physical activity in persons who are genetically susceptible to generalized or central adiposity. Design: Cross-sectional study. Setting: A London academic teaching hospital. Patients: 970 healthy female twins (mean age, 55.5 years [range, 39 to 70 years]; body mass index, 24.4 kg/[m.sup.2] [range, 16.4 to 44.0 kg/[mg.sup.2]]). There were 241 monozygotic pairs, 228 dizygotic pairs, and 32 women whose co-twin lacked complete data. Fifty-six percent of participants were of normal weight, 30% were overweight, 7% were obese, and 7% were underweight. Measurements: Total-body and central abdominal fat were measured by dual-energy x-ray absorptiometry. Physical activity was assessed by quantitative and semi-quantitative questionnaires. Data on dietary intake, socioeconomic status, smoking status, and use of hormone replacement therapy (HRT) were also gathered. Results: Total-body and abdominal central adiposity were lower with higher levels of home, sporting, and sweating-associated activity. Total-body and central abdominal fat were 5.6 kg and 0.44 kg lower, respectively, in participants who reported vigorous weight-bearing activity. Physical activity was the strongest independent predictor of total-body fat ([Beta] = -0.6 [CI, -1.06 to -0.15]; P = 0.009) and central abdominal fat ([Beta] = -0.07 [CI, -0.1 to -0.03]; P [is less than] 0.001) in a regression model that included age, diet, smoking, HRT use, and socioeconomic status. Monozygotic twin pairs who were concordant for smoking and HRT status but were discordant for moderate-intensity sport showed greater within-pair differences in total-body fat than those who were concordant, for activity level. In this model, 1 and 2 hours of moderate-intensity sport accounted for within-pair differences of 1.0 kg (P = 0.050) and 1.4 kg (P = 0.040), respectively, of total-body fat. In participants who had an overweight twin, higher levels of physical activity were still associated with 3.96-kg lower total-body fat and 0.53-kg lower central abdominal fat. Conclusions: Current physical activity predicts lower total-body and central abdominal adiposity in healthy middle-aged women. After controlling for genetic and environmental factors, the influence of physical activity was greater than that of other measured environmental factors. Participants with a genetic predisposition to adiposity did not show a lesser effect of physical activity on body fat mass., Physical activity may have a greater influence on total body fat mass in women than genetic predisposition, diet, age, smoking, or social class. Researchers compared 970 women, of whom all were twins and 37% were overweight or obese. Body fat mass and central abdominal fat mass were lower in women who undertook more regular physical activity. Even in twin-pairs with one overweight twin, an active co-twin had an average of nearly 9 pounds less body fat than an inactive co-twin.

Insulin resistance is an early phenotypic feature of nondiabetic first-degree relatives of type 2 diabetic subjects (FDR) (1,2). While intramyocellular lipid (IMCL) is a marker of insulin resistance (3), how [...]

Adiponectin is an abundant circulating adipocytokine with anti-inflammatory properties (1) linked to cardiovascular disease, type 2 diabetes, and obesity (2-5). Numerous reports (35), including the present one, confirm plasma adiponectin [...]

Oral agents, which give new options to be used in deferring insulin therapy after a regimen of diet and exercise is no longer sufficient in early type 2 diabetes, are discussed. Sulfonylurea compounds and other drugs, including alpha-glucosidase inhibitors and the thiazolidinediones, or glitazones, which can be used to control glycaemia, are reviewed.

Response to Sobel We read with interest the recent editorial by Sobel (1), wherein it is asserted that 'intensive treatment of type 1 diabetes appears to increase central obesity.' We [...]

The specific nutritional and physical activity needs of women aged 40 and over are discussed. Doctors treating such women should ensure their patients are aware of the links between lifestyle, diet and psychological well-being.

Inflammation has been implicated as an important aetiological factor in the development of both insulin resistance and type 2 diabetes mellitus. This conclusion is predominantly drawn from studies demonstrating associations between elevated (but 'normal range') levels of circulating acute phase inflammatory markers, typified by C-reactive protein (CRP), and indices of insulin resistance and the development of type 2 diabetes. There is debate as to whether these associations are independent of body fatness or, rather, an epiphenomenon of obesity, particularly central obesity, a strong predictor of insulin resistance and type 2 diabetes and an important source of inflammatory cytokines, such as interleukin-6. Some of this controversy and the inability to draw definitive conclusions from these studies relate to the fact that most studies measure body fat and its distribution indirectly using anthropometric estimates, such as Body Mass Index and waist circumference, rather than directly by dual-energy X-ray absorptiometry, computed tomography or magnetic resonance imaging. Furthermore, use of the term inflammation may be inappropriate when describing mild elevations of CRP in the 'normal range' in the absence of the other changes that characterise classical inflammatory diseases, such as a reduction in levels (or evidence of consumption) of complement proteins. Debate as to whether obesity mediates the association between circulating levels of inflammatory markers and insulin resistance can be resolved by well-designed studies using body fat measured by gold-standard methods. In this review, we present evidence to support the suggestion that body fat is the primary determinant of circulating inflammatory marker levels in the basal state and that marginally elevated levels of circulating interleukin-6 and CRP in obesity are a consequence rather than a cause of insulin resistance. The importance of genetic influences in determining both body fatness and circulating CRP levels will also be discussed. The review will conclude with a discussion of possible mechanisms linking body fat and insulin resistance to elevated circulating levels of inflammatory markers, including the possible role of the toll-like family of immune receptors.

AbstractObjective: To test in humans the hypothesis that part of the association of adiponectin with insulin sensitivity is independent of lipid availability.Research Methods and Procedures: We studied relationships among plasma adiponectin, insulin sensitivity (by hyperinsulinemic-euglycemic clamp), total adiposity (by DXA), visceral adiposity (VAT; by magnetic resonance imaging), and indices of lipid available to muscle, including circulating and intramyocellular lipid (IMCL; by 1H-magnetic resonance spectroscopy). Our cohort included normal weight to obese men (n = 36).Results: Plasma adiponectin was directly associated with insulin sensitivity and high-density lipoprotein-cholesterol and inversely with plasma triglycerides but not IMCL. These findings are consistent with adiponectin promoting lipid uptake and subsequent oxidation in muscle and inhibiting TG synthesis in the liver. In multiple regression models that also included visceral and total fat, free fatty acids, TGs, and IMCL, either alone or in combination, adiponectin independently predicted insulin sensitivity, consistent with some of its insulin-sensitizing effects being mediated through mechanisms other than modulation of lipid metabolism. Because VAT directly correlated with total fat and all three indices of local lipid availability, free fatty acids, and IMCL, an efficient regression model of insulin sensitivity (R2= 0.69, p < 0.0001) contained only VAT (part R2= 0.12, p < 0.002) and adiponectin (part R2= 0.41, p < 0.0001) as independent variables.Discussion: Given the broad range of total adiposity and body fat distribution in our cohort, we suggest that insulin sensitivity is robustly associated with adiponectin and VAT.

Objective: Little is known of the metabolism of different isoforms of adiponectin. We therefore (a) characterised the size distribution of human adiponectin in relation to gender, body composition and following a challenge with a fat meal or oral glucose in humans, and (b) studied the metabolism of isoforms of human adiponectin in rabbits.Method: Electrophoresis, blotting and chromatography were used to characterise human adiponectin in 36 healthy subjects, including 15 with at least two first-degree relatives with type 2 diabetes, before and after consumption of a fatty meal or glucose. The metabolism of column-fractionated human adiponectin was studied in rabbits, some of which were coinjected with insulin.Results: Females had a higher proportion of high molecular weight (HMW) and hexameric adiponectin (P= 0.002 and 0.004 respectively), and a lower proportion of trimers (P< 0.0001) than males. Females also showed a strong negative relationship between body fat measures and the proportion of HMW adiponectin. There were no differences in isoforms between insulin-resistant and -sensitive subjects, or following oral glucose or a fat meal. Adiponectin in rabbits had an extravascular/intravascular ratio of 0.71, and a half-life (T1/2) of 14.3 h. Metabolism was not influenced by insulin or reduction of sulphydryl bonds. HMW and trimeric isoforms had a significantly different T1/2 of 13.0 and 17.5 h respectively (P< 0.05), and these isoforms did not interconvert in vivo.Conclusions: Human adiponectin is present as trimers, hexamers and HMW forms. Females had a higher proportion and absolute amount of HMW species compared with males, and female, but not male, subjects showed a strong negative relationship between measures of body fat, and the proportion of HMW species. These isoforms did not respond to challenge in man with a fatty meal or oral glucose, and in the rabbit, to injected insulin. HMW adiponectin was more rapidly metabolised than the trimeric form, but both were stable in vivo, and did not interconvert. We conclude that human adiponectin is much longer-lived than is the case with other hormones, a finding with positive implications for the potential to supplement levels of adiponectin in man.

Objective: Abdominal fat and myocyte triglyceride levels relate negatively to insulin sensitivity, but their interrelationships are inadequately characterized in the overweight. Using recent methods for measuring intramyocyte triglyceride, these relationships were studied in men with a broad range of adiposity. Research Methods and Procedures: Myocyte triglyceride content (1H‐magnetic resonance spectroscopy of soleus and tibialis anterior muscles and biochemical assessment of vastus lateralis biopsies), regional fat distribution (DXA and abdominal magnetic resonance imaging), serum lipids, insulin action (euglycemic hyperinsulinemic clamp), and substrate oxidation rates (indirect calorimetry) were measured in 39 nondiabetic men (35.1 ± 7.8 years) with a broad range of adiposity (BMI 28.6 ± 4.1 kg/m2, range 20.1 to 37.6 kg/m2). Results: Relationships between insulin‐stimulated glucose disposal and regional body fat depots appeared more appropriately described by nonlinear than linear models. When the group was subdivided using median total body fat as the cut‐point, insulin‐stimulated glucose disposal correlated negatively to all regional body fat measures (all p≤ 0.004), serum triglycerides and free fatty acids (p< 0.02), and both soleus intramyocellular lipid (p= 0.003) and vastus lateralis triglyceride (p= 0.04) in the normal/less overweight group. In contrast, only visceral abdominal fat showed significant negative correlation with insulin‐stimulated glucose disposal in more overweight men (r= −0.576, p= 0.01), some of whom surprisingly had lower than expected myocyte lipid levels. These findings persisted when the group was subdivided using different cut‐points or measures of adiposity. Discussion: Interrelationships among body fat depots, myocyte triglyceride, serum lipids, and insulin action are generally absent with increased adiposity. However, visceral abdominal fat, which corresponds less closely to total adiposity, remains an important predictor of insulin resistance in men with both normal and increased adiposity.

Insulin resistance is associated with increased circulating lipids and skeletal muscle lipid content. Chronic nicotinic acid (NA) treatment reduces insulin sensitivity and provides a model of insulin resistance. We hypothesized that the reduction in insulin sensitivity occurs via elevation of circulating nonesterified fatty acids (NEFAs) and an increase in intramyocellular lipid (IMCL). A total of 15 nondiabetic males (mean age 27.4 ± 1.6 years) were treated with NA (500 mg daily for 1 week, 1 g daily for 1 week). Insulin sensitivity (glucose infusion rate [GIR]) was determined pre- and post-NA by euglycemic-hyperinsulinemic clamp. Substrate oxidation was determined by indirect calorimetry. Skeletal muscle lipid was assessed by estimation of long-chain acyl-CoA (LCACoA) and triglyceride (TG) content and by 1H-magnetic resonance spectroscopy quantification of IMCL (n = 11). NA reduced GIR (P= .03) and nonoxidative glucose disposal (P< .01) and increased fasting NEFAs (P= .01). The decrease in GIR related significantly to the increase in fasting NEFAs (r2= .30, P= .03). The intrasubject increase in basal and clamp fat oxidation correlated with the decrease in GIR (r2= .45, P< .01 and r2= .63, P< .01). There were no significant changes in muscle LCACoA, TG, or IMCL content. Therefore, induction of insulin resistance by NA occurs with increased availability of circulating fatty acids to muscle rather than with increased muscle lipid content.

Objective:Computed tomography (CT) and magnetic resonance imaging, the most accurate methods of abdominal fat measurement, have been applied using a number of protocols, ranging from single‐slice area determination to multiple‐slice volume calculation. The aim of this study was to assess the validity of single‐slice CT for abdominal fat area measurement by estimating the intra‐subject variability in abdominal fat areas and comparing the ranking of subjects across four contiguous abdominal levels. Research Methods and Procedures:Nineteen premenopausal women (age, 35.3 ± 1.4 years; mean ± SE) were studied. CT was used to measure intra‐abdominal fat (IAF) area, percentage of total intra‐abdominal area (%IAF), subcutaneous abdominal fat (SAF) area, and IAF/SAF at four adjacent cross‐sectional lumbar levels (L2–L4). Intra‐subject variability (percentage) was defined as SD/mean × 100. Total body fat was measured by DXA, which was further analyzed for central abdominal fat. Results:Mean body mass index was 24.9 ± 1.0 kg/m2. The average (range) intra‐subject variability was 28% (8% to 61%) for IAF, 46% (19% to 124%) for %IAF, 26% (14% to 38%) for SAF area, and 19% (7% to 71%) for IAF/SAF. The pattern of this variability was not uniform between subjects, because their ranking by IAF area was markedly different at each CT level. Discussion:We demonstrated significant intra‐subject variability in CT‐measured adipose tissue areas across four predetermined sites. This resulted in a difference in the ordering of subjects by IAF at each of the four imaging sites, suggesting that the usefulness of single‐slice CT in the assessment of abdominal adiposity in premenopausal women may be limited, particularly when performed for the purpose of making comparisons between subjects based on abdominal fat area.

Objective:Insulin resistance is closely associated with two disparate aspects of lipid storage: the intracellular lipid content of skeletal muscle and the magnitude of central adipose beds. Our aim was to determine their relative contribution to impaired insulin action. Research Methods and Procedures:Eighteen older (56 to 75 years of age) men were studied before elective knee surgery. Insulin sensitivity (M/ΔI) was determined by hyperinsulinemic–euglycemic clamp. Central abdominal fat (CF) was assessed by DXA. Skeletal muscle was excised at surgery and assayed for content of metabolically active long‐chain acyl‐CoA esters (LCAC). Results:Significant inverse relationships were observed between LCAC and M/ΔI (R2= 0.34, p= 0.01) and between CF and M/ΔI (R2= 0.38, p= 0.006), but not between CF and LCAC (R2= 0.0005, p= 0.93). In a multiple regression model (R2= 0.71, p< 0.0001), both CF (p= 0.0006) and LCAC (p= 0.0009) were independent statistical predictors of M/ΔI. Leptin levels correlated inversely with M/ΔI (R2= 0.60, p= 0.0002) and positively with central (R2= 0.41, p= 0.006) and total body fat (R2= 0.63, p= 0.0001). Discussion:The mechanisms by which altered lipid metabolism in skeletal muscle influences insulin action may not be related directly to those linking central fat and insulin sensitivity. In particular, it is unlikely that muscle accumulation of lipids directly derived from labile central fat depots is a principal contributor to peripheral insulin resistance. Instead, our results imply that circulating factors, other than nonesterified fatty acids or triglyceride, mediate between central fat depots and skeletal muscle tissue. Leptin was not exclusively associated with central fat, but other factors, secreted specifically from central fat cells, could modulate muscle insulin sensitivity.

AbstractHomeostasis model assessment (HOMA) provides indices of insulin secretion (?) and insulin resistance (R) derived from fasting plasma glucose (FPG) and fasting plasma insulin (FPI) levels. However, these indices could not account for a significant heritability of fasting plasma glucose (FPG) (h2= 0.75, P < 0.01) in a group of 214 female twins. This result is consistent with a misclassification between effects due to insulin secretion and resistance in the HOMA indices. We report here evidence of such misclassification in the HOMA indices and describe a minor modification to the model which corrects it. Direct measures of insulin resistance (euglycaemic clamp) and secretion (i.v. glucose bolus) were obtained in 43 non-diabetic subjects. Heritability was estimated by statistical modelling of genetic and environmental influences in data from 214 non-diabetic female subjects. Modified HOMA (HOMA?) indices were obtained from ?? = (Ln(FPI)?c)/FPG and R? = (Ln(FPI)?c)* FPG where c is a constant derived from regression analysis of Ln(FPI) vs FPG. Indices from both models correlated with the direct measures similarly (r = 0.63 (R), 0.49 (R?), 0.45 (?), 0.39 (??), all P < 0.01). Directly measured insulin resistance and secretion were not significantly correlated (r = 0.13, P = 0.21). However, unmodified HOMA- and R were strongly related (r = 0.78, P < 0.0001 vs 0.13) demonstrating substantial misclassification. The relationship between ?? and R? (r = 0.13) was not different from that between the two direct measures and significant heritability of ?? (h2= 0.68, P < 0.01) and R? (h2= 0.59, P < 0.05) was evident in the twin data. The proposed modification to HOMA significantly reduces misclassification and reveals separate components of insulin resistance and insulin secretion in the heritability of FPG. Twin Research (2000) 3, 148?151.

AbstractObesity, insulin resistance and disturbed glucose metabolism cluster within the Insulin Resistance Syndrome (IRS). Whether this reflects shared genetic or environmental factors detectable in ?normal? populations (not selected for IRS features) is unknown. This study estimated (i) genetic influences on IRS traits and (ii) shared and specific genetic and environmental factors on the relationships between these traits in healthy female twins. Fasting insulin, glucose, total and central fat were measured in 59 monozygotic (MZ) and 51 dizygotic (DZ) female twin pairs aged ( ? SD) 52 ? 13 years. Body fat was measured by dual-energy X-ray absorptiometry, insulin resistance and secretion by a modified homeostasis model assessment. Using intraclass correlation coefficients and univariate model-fitting analyses, genetic influences were found in total fat, central fat, insulin resistance, fasting glucose and insulin secretion, with genetic factors explaining 64, 57, 59, 75 and 68% of their variance, respectively, using the latter technique. In matched analysis intra-pair differences in total and central fat related to intra-pair differences in insulin resistance (r2 = 0.19, P < 0.001). Multivariate model-fitting showed a close genetic relationship between total and central fat (r = 0.88). The genetic correlation between IR and central fat (0.41) was significantly greater than that for total fat (0.24), suggesting that central fat is not only a predictor of, but shares considerable genetic influence with, insulin resistance. In Cholesky analysis, these genetic influences were separate from those shared between central and total fat. In conclusion, both shared and specific genetic factors regulate components of the IRS in healthy females. However, there were discrete genetic influences on -cell insulin secretion, not shared with other IRS components, suggesting that a separate genetic propensity exists for Type2 diabetes. These findings suggest we may understand the genetic and environmental influences on IRS from the study of the normal population.

Four‐day food records, body mass index and glycosylated haemoglobin levels were measured in 212 subjects with established non‐insulin‐dependent diabetes, who volunteered for a trial of educational programmes. Of these subjects, 79% were above their ideal body weights and 75% of subjects had a glycosylated haemoglobin level that was above the normal range. Ninety‐five per cent of subjects reported a total fat intake of greater than 30% of their total energy intake, and 80% of subjects reported a total carbohydrate intake of less than 50% of their total energy intake. These results suggest that the current methods for the management of non‐insulin‐dependent diabetes do not achieve optimal long‐term dietary results.

Before insulin therapy is begun, patients with diabetes are often admitted to hospital. In a retrospective study we have reviewed the initiation of insulin therapy in 54 unselected outpatients (12 of whom were insulindependent), when the initial stabilization of therapy was performed predominantly by nurse educators. Most patients found the procedure satisfactory; only one subject indicated dissatisfaction with the regimen and only two indicated that they would have preferred admission to hospital. No patient experienced an acute hypoglycaemic or hyperglycaemic problem that required admission to hospital nor was emergency intervention required during the 12 months that followed the initial stabilization period of insulin therapy. Metabolic control, as measured by glycosylated haemoglobin levels, improved in the majority of both insulindependent and non‐insulin‐dependent patients after 12 months of insulin therapy. A retrospective cost analysis that compared the cost of the outpatient procedure with the cost (hospital‐bed costs only) of initiating insulin therapy in a similar group of patients who were admitted to hospital, indicated a saving of $1857 for each outpatient. We conclude that the outpatient initiation of insulin therapy is feasible where the facilities for education about diabetes exist, that it is safe, achieves satisfactory metabolic control, is acceptable to most patients, and offers a considerable saving in costs.

ABSTRACT The aetiology and management of diabetic impotence is well‐documented; the effects of diabetes on female sexuality are not so clear. In this study, 48 diabetic women were assessed clinically and answered detailed sexual questionnaires during a semistructured interview with a sexual counsellor. Twenty‐four of the women reported one‐or‐more sexual dysfunctions: decreased libido, slow arousal, inadequate lubrication, anorgasmia or dyspareunia. There was no significant relationship between the presence of dysfunction and recent glycaemic control, the duration of diabetes, the presence of clinical complications or of neuropathy alone, or the attitude to sexuality. The sexual dysfunction(s) were present at the onset of diabetes in the majority of those so affected (17 of 24 patients), or were attributed to other causes in the remainder. It is suggested that sexual dysfunction in diabetic women should be treated actively as in “normal” women, since diabetes is not the major aetiological factor.

In spite of maximal doses of sulphonylurea agents, patients with poorly controlled non‐insulin dependent diabetes (NIDDM) often do not have improved metabolic control after the introduction of insulin therapy. We have assessed 22 patients with NIDDM who commenced insulin therapy in order to identify those characteristics which were associated with an improvement in glycaemic control. Twelve months after the commencement of insulin therapy, 14 (64%) patients showed a decrease in glycosylated haemoglobin (HbA1) levels; 12 of the 14 (55%) patients had achieved HbA, levels that were considered to reflect acceptable glycaemic control (HbA, less than or equal to 11%; reference range, 6%–9%). The HbA, levels in the other patients either remained unchanged or had increased (one subject). When the subjects who had achieved good glycaemic control with insulin therapy were compared with the remainder of the group, a failure to improve with insulin therapy was associated with a longer duration of diabetes, greater obesity and higher levels of cholesterol and triglycerides before the commencement of insulin therapy. Greater obesity and high levels of circulating lipids were found by means of multiple linear regression analysis to correlate independently with a poor response to insulin therapy. We conclude that standard insulin therapy can improve the majority of patients with poorly controlled NIDDM. However, there is a substantial number of patients, who tend to be obese and have high levels of circulating lipids, whose condition does not improve with insulin therapy, or who require more aggressive dosage increases than are used as a routine.