Non-invasive screening, staging and management of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus patients: what do we know so far ?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus (T2DM). Indeed, T2DM and liver steatosis share common pathophysiological mechanisms, and one can lead to the other. MAFLD can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis as well as hepatocellular carcinoma (HCC). Because of the lack / disparity of guidelines for MAFLD screening, which is asymptomatic in its early stages, it is not rare that diabetic patients are belatedly diagnosed with NASH cirrhosis or HCC. We therefore recommend systematic non-invasive tests (NITs) that calculate an estimate of the risk based on readily available anthropometric and biological parameters. These include the fatty liver index (FLI) for steatosis detection and at least one of the following for fibrosis: non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4) or Hepamet fibrosis score (HFS). Indeed, NFS and FIB-4 are the best predictors of liver-related events, while FIB-4 and HFS correlate with overall mortality. Systematic literature review found only few retrospective or cross-sectional studies using NITs for systematic steatosis and fibrosis screening in T2DM patients, with a crucial need for prospective studies. This screening strategy will allow targeted patients to be referred for further liver investigation (e.g. ultrasound, elastometry) and care. Current treatment modalities of MAFLD in T2DM patients range from lifestyle and dietary interventions to specific glucose-lowering drugs that recently showed some benefits regarding MAFLD, such as pioglitazone, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Other treatments are currently under investigation.

Clinical and biochemical characteristics and analysis of risk factors for euglycaemic diabetic ketoacidosis in type 2 diabetic individuals treated with SGLT2 inhibitors: A review of 72 cases over a 4.5-year period.

BACKGROUND AND AIMS: To study euglycemic diabetic ketoacidosis (euDKA) outcomes associated with sodium-glucose co-transporter 2 inhibitors (SGLT2is) METHODS: Review of 72 euDKA cases in T2DM between September 2015 and January 2020 (PUBMED). RESULTS: euDKA could occur at any time during SGLT2is treatment, with nausea, abdominal pain and vomiting as main symptoms. Hyperglycemia did not correlate with pH and ß-hydroxybutyrates. Low pH and high ß-hydroxybutyrates were significantly associated with euDKA. In biguanides users, acidosis was unrelated to lactic acidosis. euDKA occurred during fasting, surgery, acute infection, insulin deprivation (endogenous or exogenous). CONCLUSIONS: These data support avoidance of euDKA risk states in SGLT2i users.

[Diabetic euglycemic ketosis or ketoacidosis in individuals with type 2 diabetes treated by SGLT2 inhibitors: A series of Belgian clinical cases]. / Cétose ou acidocétose diabétique euglycémique chez des patients diabétiques de type 2 traités par inhibiteurs du SGLT2 : une série de cas cliniques en Belgique.

INTRODUCTION: Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are new therapeutic agents that improves the management of type 2 diabetes. Clinical trial results for SGLT2i have shown a reduction in blood glucose levels and a decrease in significant cardiovascular and renal complications related to diabetes. However, rare adverse events such as diabetic ketoacidosis have been reported in these clinical trials and in "real life". These ketoacidosis were atypical because the hyperglycemia was less severe than in traditional acute diabetes, hence the name of "euglycemic" ketoacidosis. We detail a series of local cases associated with the use of SGLT2i in type 2 diabetic patients. METHODS: This was a retrospective consecutive case study, with a review of medical records from 2016 to 2019. We identified 7 single episodes of "euglycemic" ketoacidosis associated with SGLT2i use in individuals with type 2 diabetes. RESULTS: Seven cases of type 2 diabetic individuals (M/F: 5/2) aged from 51 to 74years old were analysed. All had symptoms of hyperketonemia (fruity smelling breath, nausea or lack of appetite) and an increase level of capillary ß-hydroxybutyric acid despite a glycaemia between 112 and 280mg/dL. The risk factors for ketoacidosis identified in these patients were: prolonged fasting, infection, dehydration and significantly decreased in insulin secretory function (according to the HOMA model), revealing endogenous insulinopenia before ketoacidosis. CONCLUSION: The increasing use of SGLT2i in individuals with type 2 diabetes is likely to increase the number of ketoacidosis cases. It is essential to recognise this complication and prevent it according to each patient's risk factors.

Frailty score for elderly patients is associated with short-term clinical outcomes in patients with ST-segment elevated myocardial infarction treated with primary percutaneous coronary intervention.

OBJECTIVE: Consistent with the aging population in the Western world, there is a growing number of elderly patients with ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) is the recommended reperfusion strategy in elderly patients; risk models to determine which of these patients are prone to have poor clinical outcomes are, however, essential. The purpose of this study was to assess the association between frailty and short-term mortality and PCI-related serious adverse events (SAE) in elderly patients. METHODS: All STEMI patients (aged ≥70 years) treated with primary PCI in 2013-2015 at the Leiden University Medical Centre were assessed. The Safety Management Programme (VMS) score was used to identify frail elderly patients. The primary endpoint was 30-day all-cause mortality; the secondary endpoint included 30-day clinical death, target vessel failure, major bleeding, contrast induced kidney insufficiency and stroke. RESULTS: A total of 206 patients were included (79 ± 6.4 years, 119 [58%] male). The VMS score was ≥1 in 28% of all cases. Primary and secondary endpoint rates were 5 and 23% respectively. VMS score ≥1 was an independent predictor for both 30-day mortality (odds ratio [OR] 9.6 [95% confidence interval, CI 1.6-56.9] p-value = 0.013) and 30-day SAE (OR 2.9 [95% CI 1.1-7.9] p-value = 0.038). CONCLUSIONS: VMS score for frailty is independently associated with short-term mortality and PCI-related SAE in elderly patients with STEMI treated with primary PCI. These results suggest that frailty in elderly patients is an important feature to measure and to be taken into account when developing risk models.

Weight loss at a high cost: Orlistat-induced late-onset severe kidney disease.

AIM: This report describes a case of kidney failure secondary to orlistat, a lipase inhibitor commonly used in the treatment of obesity. CASE REPORT: An 80-year-old man with type 2 diabetes who was being treated with orlistat developed rapidly progressive kidney failure. Low-grade albuminuria argued against diabetic nephropathy. Renal biopsy showed tubulointerstitial nephritis associated with numerous calcium oxalate crystals. Enteric hyperoxaluria was attributed to the orlistat treatment. The latter was stopped and the patient received calcium supplements. Six months after orlistat withdrawal, oxaluria was normalized and kidney function stabilized. CONCLUSION: Oxalate nephropathy may result from hyperoxaluria secondary to orlistat treatment. This suggests that kidney function and oxaluria be closely monitored in patients taking orlistat.

[Levels of target achievement for major modifiable cardiovascular risk factors in Belgium]. / Niveaux d'atteinte des valeurs cibles thérapeutiques pour des facteurs majeurs modifiables du risque cardiovasculaire en Belgique.

Cardiovascular disease (CVD) is the main cause of premature mortality in Europe. The burden of CVD could be reduced by controlling the major modifiable CVD risk factors (dyslipidaemia, arterial hypertension, hyperglycaemia, smoking, and physical inactivity) through lifestyle and dietary changes and appropriate drug therapies. The objective of this article is to assess the level of target achievement for key modifiable CVD risk factors in Belgium by referring to the data from four recent studies. The overall results show that the main CVD risk factors are poorly controlled in patients with established CVD and in patients at high CVD risk. Therapeutic targets may be incompletely reached because of the suboptimal implementation of European guidelines for CVD prevention in routine clinical practice (insufficient lifestyle and dietary adaptations; poor applications of drug therapy to control blood pressure, dyslipidaemia and hyperglycaemia) or because of the insufficient efficacy of currently available treatment options in some patients. This review provides clear and updated evidence for non-target achievement for all major risk factors, with four different study designs and inclusion criteria; it highlights the need for a more comprehensive and intensive application of recommendations of the European guidelines for CVD prevention in Belgium.

What is the phenotype of patients with gastrointestinal intolerance to metformin?

BACKGROUND: A substantial minority of type 2 diabetes mellitus (T2DM) patients treated with metformin develop severe gastrointestinal (GI) symptoms leading to drug discontinuation, depriving them of the potentially cardioprotective pleiotropic effects of this first-line oral agent. At present, it is unclear whether treating diabetes without being able to ever use metformin alters cardiovascular outcomes. PATIENTS AND METHODS: From a population of 773 consecutive T2DM outpatients, the cardiometabolic phenotypes of 83 patients who discontinued metformin due to GI intolerance (Met-Intol cases) were compared with those of 332 age- and gender-matched metformin-tolerant (Met-Tol) controls, amounting to a case: control ratio of 1:4. RESULTS: Mean age (SD) was 70 (13) (male:female: 46:54). Metformin intolerance was associated with a reduced prevalence of macroangiopathy (P=0.0486), mainly due to a lower prevalence of CAD (-34%; P=0.0374). Met-Intol cases more often belonged to blood group A and subgroup A Rh+, with 50% and 66% relative increases (P=0.0039 and P=0.0005), respectively. There were twice as many non-right-handers among the Met-Intol (18% vs. 9%; P=0.0262), and this group also had significantly higher serum ferritin and LDL cholesterol levels. Statins/fibrates were used by 66%/19% of Met-Tol vs. 48%/18% of Met-Intol (P=0.0051 for statins). On the other hand, there were no differences between groups as regards smoking, diabetes duration, HbA1c, BMI, blood pressure, waist size, fat mass, visceral fat, liver steatosis, the metabolic syndrome, eGFR, albuminuria, erectile dysfunction and microangiopathy. CONCLUSION: Intolerance to metformin represents an unforeseen phenotype in T2DM patients characterized by a low rate of ischaemic heart disease, left-handedness, ABO group imbalance and an iron load.

Age and living in an urban environment are major determinants of diabetes among South Kivu Congolese adults.

OBJECTIVES: This study aimed to determine the risk factors for diabetes mellitus (DM) in the eastern part of the Democratic Republic of Congo. METHODOLOGY: Multilevel sampling identified 200 households (444 adults aged ≥ 20 years) from 20 neighbourhoods in the city of Bukavu, and 90 households (255 adults aged ≥ 20 years) from 10 villages in the Kaziba (South Kivu) chiefdom (the South Kivu VITARAA study). DM was defined as a personal history of the disorder or a casual glycaemia greater or equal to 200 mg/dL. Standardization according to age and sample readjustment based on the urban-rural distribution of the population was applied accordance with the typical Congolese population. The probability of DM was assessed by multiple logistic regressions. RESULTS: Total prevalence of DM was 3.5%. DM was significantly more prevalent in urban areas (age-standardized prevalence: 4.0%) than in rural areas (1.7%). City-dwelling DM patients were characterized by higher rates of indices of abdominal obesity (P < 0.05) whereas, in rural areas, no patients were obese. In the study group as a whole, only 25.0% of diabetic patients were obese. On multivariate analyses, only age [adjusted OR (95% CI): 4.79 (1.60-14.25); P = 0.004] was independently associated with the prevalence of DM, while the effect of obesity was not significant [2.64 (0.99-7.02); P = 0.051]. CONCLUSION: Age and living in an urban environment appeared to be major determinants of DM in South Kivu. Also, obesity prevalence was relatively low in these diabetic patients, confirming the peculiar, relatively lean, phenotype of type 2 DM in indigenous sub-Saharan Africans.

Predictive factors associated with primary failure to exenatide and non goal attainment in patients with type 2 diabetes.

OBJECTIVE: We prospectively analysed HbA1c changes after 12 months of exenatide therapy and determined which baseline clinical and/or biological factors predict response. RESEARCH DESIGN AND METHODS: Open-label cohort of 41 subjects with type 2 diabetes (56% male) poorly-controlled on maximally-tolerated oral dual therapy. Age (mean ± 1SD) was 60 ± 10 years, and known diabetes duration 11 ± 8 years (mean ± 1SD). Biometric changes in weight, body mass index (BMI), waist circumference (WC), HOMA modeling (Homeostasis Model Assessment) of ß-cell function (HOMA-B) and insulin sensitivity (HOMA-S) as well as in HbA1c were assessed at baseline, and after 6 or 12 months exenatide therapy. Patients were divided into three groups: goal-achievers (GA, n = 15), defined as achieving HbA1c ≤ 7.5% (58 mmol/mol) at 12 months; nongoal- achievers (NGA, n = 16; HbA1c > 7.5% (58 mmol/mol) at 12 months); and primary failure to exenatide therapy (early lack of efficacy; PF, n = 9). Non-responders represented the combined NGA plus PF patients. RESULTS: The addition of exenatide to maximally-tolerated oral dual therapy led to target HbA1c attainment (≤ 7.5% (58 mmol/mol) at 1 year) in 37% of cases, associated with reduction in weight, BMI and waist circumference. GA were older than non-responders (64 ± 9 vs. 57 ± 10 years, p = 0.032). Diabetes duration was comparable. Baseline HbA1c was significantly lower in GA (8.3 ± 0.9 vs. 9.5 ± 0.9% in non-responders; p < 0.001). Baseline HOMA-B and HOMA-S were comparable, while HOMA product (BxS) was higher in GA (17 ± 6 vs. 14 ± 6% in non- responders, p = 0.04). At 12 months, HbA1c reached 7.0 ± 0.6% in GA vs. 9.0 ± 1.3% in non-responders. Weight, BMI and waist circumference decreased in both groups. In GA and non-responders, there was a marked relationship between baseline HbA1c and absolute decrement in HbA1c over the study period. Logistic regression demonstrated that baseline HbA1c was the strongest predictor for target attainment following exenatide therapy (p < 0.001), with age to a lesser degree (p = 0.089). CONCLUSION: Baseline HbA1c is a major predictor of response to exenatide treatment, defined as target HbA1c (≤ 7.5%, 58 mmol/mol) attainment. The lower the baseline HbA1c, the greater the likelihood of reaching the target HbA1c at 12 months, even though patients with higher baseline HbA1c benefited from the largest absolute reduction in HbA1c levels.

Exenatide improves weight loss insulin sensitivity and ß-cell function following administration to a type 2 diabetic HIV patient on antiretroviral therapy.

The use of retroviral drugs in the treatment of infection by human immunodeficiency virus (HIV) is associated, especially for first generations, with side effects such as lipodystrophy, fatty liver and insulin resistance, which may trigger secondary diabetes or worsen existing diabetes. The use of Glucagon-Like Peptide-1 in obese patients with type 2 diabetes on HIV retroviral as an alternative to insulin therapy is not documented; we report the case of a 47-year-old treated with exenatide when insulin was discontinued. During the first year of treatment, exenatide, in combination with metformin and repaglinide, led to a weight loss of 14 kg and fat mass and waist circumference were respectively reduced from 31 to 25.5% and from 114 to 103 cm. Homeostatic model assessment (HOMA) was used to calculate ß-cell secretion which increased from 50 to 78% and insulin sensitivity which increased from 28 to 51%, reflecting a decrease in HbA(1c) by 1.9%. Exenatide may be a new therapeutic option for HIV-infected type 2 diabetes patients undergoing retroviral therapy.

Statin therapy and cataract in type 2 diabetes.

BACKGROUND: It was recently reported that the prolonged use of statins may predispose to incident cataract in the general population. Cataract is a frequent comorbidity of diabetes, and statins are widely prescribed in patients with type 2 diabetes (T2D) both for primary and secondary cardiovascular prevention. For this reason, this study aimed to assess whether or not the use of statins was associated with an increased prevalence of cataract in such a high-risk population and, conversely, whether or not there was greater usage of statins, or any other lipid-lowering drugs, in T2D patients with cataract. PATIENTS AND METHODS: This was a cross-sectional analysis of 780 T2D outpatients, with a mean age (± 1 SD) of 64 ± 12 years and diabetes duration of 13 ± 9 years. Diabetic retinopathy (DR) was found in 23%, and cataract was diagnosed in 16.8% (n=131). Age and diabetes duration of the patients with cataract were significantly higher than those of patients without cataract (n = 649): 75 ± 9 vs 62 ± 11 years, and 20 ± 11 vs 12 ± 8 years, respectively (both P < 0.0001). HbA(1c) was non-significantly higher in the cataract group: 7.75 ± 1.55% vs 7.57 ± 1.49% (NS). RESULTS: Statins, fibrates and/or ezetimibe use did not differ between patients with and without cataract, nor was cataract prevalence higher in statin users (n=435) vs non-users (n = 345). Statin use in patients with cataract was not higher than in cataract-free subgroups with mean age (n=218) or with both mean age and diabetes duration (n = 161) similar to those of patients with cataract. CONCLUSION: In this cross-sectional analysis of a large diabetic population at very high risk of both DR and cataract, chronic therapy with statins was not cataractogenic, and the presence of cataract was not associated with more statin or other lipid-lowering drug use. This suggests that the benefits of statin therapy in T2D may far outweigh any potential ocular drawbacks as a side effect which, in any case, were not supported by our findings.

Do high ferritin levels confer lower cardiovascular risk in men with Type 2 diabetes?

AIMS: High ferritin levels are associated with insulin resistance and liver steatosis, both thought of as emerging cardiovascular risk factors. The association between ferritin and cardiovascular disease is poorly documented in cardiometabolic states with higher cardiovascular risk, such as diabetes and metabolic syndrome. We therefore characterized a cohort of males with Type 2 diabetes mellitus (T2DM) according to ferritin levels and prevalent macroangiopathy. METHODS: The presence of overall macroangiopathy, peripheral and/or coronary artery disease was documented in 424 consecutive T2DM males, who were divided according to ferritin quartiles (Q) as follows: QI-III, normal ferritin (NF; n=318), mean+/-1 sd ferritin 133+/-72 ng/ml; and QIV patients, high ferritin (HF; n=106), ferritin 480+/-228 ng/ml. RESULTS: Age, age at diabetes diagnosis, smoking, ethanol intake, body mass index, waist circumference, blood pressure and presence of metabolic syndrome did not differ between groups. However, the prevalence of macroangiopathy was unexpectedly much lower in patients with high ferritin, as follows: 25% vs. 43% for overall macroangiopathy; 7% vs. 16% for peripheral artery disease; and 16% vs. 31% for coronary artery disease (P=0.0009, P=0.0140 and P=0.0035, respectively, vs. NF patients). Insulin resistance index and prevalence of liver steatosis were higher in HF compared with NF patients as follows: 2.17% vs. 1.89% and 78% vs. 64% (P=0.0345 and P=0.0059, respectively). Liver enzymes (aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase) were significantly higher in HF, by 33%, 42% and 72%, respectively (all P<0.0002), suggesting a higher prevalence of steatohepatitis. Glycated haemoglobin, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, urate, high-sensitivity C-reactive protein and albuminuria were not different between groups. CONCLUSIONS: Our results demonstrate that T2DM males with high ferritin levels exhibit a markedly decreased prevalence of macroangiopathy, despite more severe insulin resistance and higher markers of steatohepatitis. High ferritin levels and/or steatosis may thus paradoxically confer a lowered cardiovascular risk in diabetic males.

Six-month exenatide improves HOMA hyperbolic product in type 2 diabetic patients mostly by enhancing beta-cell function rather than insulin sensitivity.

OBJECTIVE: This study aimed to determine whether or not the improvement of glycaemic control with 6-month exenatide therapy in type 2 diabetic patients with secondary failure to combined oral therapy is related to amelioration of ß-cell function and/or insulin sensitivity and their combined product. RESEARCH DESIGN AND METHODS: Thirty-three patients with type 2 diabetes were investigated. Their ß-cell function and insulin sensitivity were measured using Homoeostasis Model Assessment [HOMA-B, HOMA-S and HOMA hyperbolic product (BxS)]. Additional endpoints included changes in weight, HbA(1c) and plasma adiponectin, as well as baseline clinical and biological characteristics, as potential predictors of HbA(1c) response. RESULTS: After 6 months, unadjusted HOMA-B increased from 33 ± 24% to 43 ± 23% (P=0.0210), whereas there was no significant change in HOMA-S (from 58 ± 35% to 61 ± 40%). The hyperbolic product increased by a relative 70% (from 15 ± 7% to 22 ± 15%; P=0.0055). Body mass index decreased from 32.2 ± 5.1 kg/m(2) to 31.0 ± 4.8 kg/m(2) (P<0.0001) and HbA(1c) from 8.8 ± 1.0% to 7.6 ± 1.2% (P<0.0001). No change was observed in adiponectin concentrations. Higher baseline HbA(1c) values were a significant predictor of therapeutic response. CONCLUSION: Exenatide significantly increased HOMA-B and hyperbolic product over a 6-month treatment period with no overall change in insulin sensitivity, despite weight loss. Thus, improved ß-cell function rather than increased insulin sensitivity accounts for the bulk of HbA(1c) reduction following 6 months of exenatide treatment.

Implications of the ACCORD lipid study: perspective from the Residual Risk Reduction Initiative (R(3)i).

Most type 2 diabetes patients remain at high residual risk of cardiovascular events despite best treatment. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial aimed to address this challenge, by evaluating whether intensive control of glycaemia and high blood pressure, or as in ACCORD Lipid, extending lipid treatment with the combination of fenofibrate plus simvastatin, could impact this risk. ACCORD Lipid showed that treatment beyond low-density lipoprotein cholesterol was not appropriate for most type 2 diabetes patients. However, a subgroup analysis did suggest additional benefit in patients with atherogenic dyslipidaemia, the combination of high baseline triglycerides (>or=204 mg/dL or 2.3 mmol/L) and low baseline plasma levels of high-density lipoprotein cholesterol (

Dietary cassava, beta-cell function and hyperbolic product loss rate in type 2 diabetes patients from South Kivu.

OBJECTIVE: Cassava, a major carbohydrate source in Africa, contains potentially diabetogenic chemicals, although its consumption is not associated with incident diabetes. As it is not known whether cassava intake impairs residual beta-cell function in patients with type 2 diabetes (T2D), our study compared the metabolic phenotypes of diet- and/or oral antidiabetic drug (OAD)-treated T2D patients in South Kivu (Democratic Republic of the Congo) with [Cassava (+); n=147] and without [Cassava (-); n=46] self-reported cassava consumption. DESIGN & METHODS: A total of 193 patients [male:female (%) 37:63; mean +/-1 SD age: 56+/-11 years] were interviewed to determine the frequency and distribution of eight major dietary carbohydrate (CHO) sources (cassava, plantain, rice, maize, bread, sorghum, potatoes and legumes). Fasting glucose, insulin and lipid levels were obtained after an overnight fast and OAD discontinuation. Cassava (+) and Cassava (-) groups were compared for HOMA indices of insulin sensitivity (S), beta-cell function (B), hyperbolic product (B x S) and B x S loss rate (B x S LR). RESULTS: Diabetes duration was 6+/-7 years, age at diabetes diagnosis was 51+/-11 years and BMI was 25+/-5 kg/m(2). Cassava intake was reported by 76% of patients, and amounted to 29+/-11% of their daily CHO intake. The Cassava (-) group ate more plantain, maize, bread and potatoes, and less sorghum. Age, gender and age at diabetes diagnosis did not differ between Cassava (+) and (-) patients, nor did BMI, fat mass, waist circumference, lipid profile and metabolic syndrome prevalence. HOMA indices of S, B, B x S and B x S LR did not differ significantly between groups-Cassava (+) vs (-): S, 114+/-56% vs 114+/-60%; B, 34+/-30% vs 39+/-32%; B x S, 38+/-35% vs 40+/-31%; and B x S LR, 1.19+/-0.84% vs 1.09+/-0.65% per year-nor did the glucose-lowering modalities. CONCLUSION: Cassava consumption in South Kivu is not associated with changes in T2D phenotype or in the glucose homoeostasis determinants S, B, B x S and B x S LR. Cassava consumption does not accelerate beta-cell function loss in such a population, whose markedly compromised glucose homoeostasis renders them vulnerable to environmentally acquired beta-cell impairment.

Handedness, insulin sensitivity and pancreatic B-cell function in Type 2 diabetes.

BACKGROUND: Laterality is associated with various health conditions. No study has addressed the influence of handedness on Type 2 diabetes mellitus (T2DM) phenotype, including glucose homeostasis, glucose-lowering therapies and metabolic control. METHODS: Five hundred and seventy-six consecutive adult T2DM outpatients underwent homeostasis model assessment (HOMA) of pancreatic B-cell function (B), insulin sensitivity (S), hyperbolic product (B x S) and age-standardized B x S deficit. Right-handed patients (87.5%; RH; n = 504) had similar age, gender, diabetes duration and education than non-right-handed patients (12.5%; non-RH; n = 72). RESULTS: Non-RH were more insulin-sensitive: 66% (39%) vs. 52% (36%) [mean (1 sd); P = 0.0024] and had significantly higher B x S and lower age-adjusted B x S deficit: 35% (20%) vs. 26% (17%) and 1.08% (0.40%) vs. 1.32% (0.55%)/year (non-RH; P = 0.0005 and P < 0.0001, respectively). CONCLUSIONS: Non-right-handed T2DM patients are more insulin-sensitive, have higher hyperbolic product and less age-standardized B x S deficit. These may modulate glucose-lowering therapy requirements and glycaemic control.