The Microalbuminuria Education Medication and Optimisation (MEMO) study: 4 years follow-up of multifactorial intervention in high-risk individuals with type 2 diabetes.

AIMS: The Microalbuminuria Education Medication and Optimisation (MEMO) study, revealed improved cardiovascular risk and glycaemic control with 18 months of intensive multifactorial intervention in high-risk people with type 2 diabetes, without any increase in severe hypoglycaemia. Our aim was to assess longer-term outcomes at 4-year follow-up in these participants. METHODS: Some 189 individuals with type 2 diabetes and microalbuminuria were recruited from a multi-ethnic population in Leicestershire, UK. The intervention group (n = 95) received multifactorial intervention with self-management education, and the control group (n = 94) received usual care. The primary outcome was change in HbA1c , and secondary outcomes were blood pressure (BP), cholesterol, microalbuminuria, estimated GFR, cardiovascular risk scores and major adverse cardiovascular events. RESULTS: Some 130 participants (68.7%), mean (sd) age 60.8 (10.4) years, duration of diabetes 11.5 (9.7) years, completed 4 years of follow-up. Mean change [95% confidence intervals (CI)] in HbA1c over 4 years was greater with intensive intervention compared with control (-3 mmol/mol, 95% CI -4.95,-1.11; -0.4%, 95% CI -0.67,-0.15; P = 0.002). Significant improvements over the 4 years were also seen in systolic BP (-7.3 mmHg, 95% CI -11.1, -3.5; P < 0.001), diastolic BP (-2.9 mmHg, 95% CI -5.4, -0.3; P = 0.026), cholesterol (-0.3 mmol/l, 95% CI -0.52,-0.12; P = 0.002), and 10-year coronary heart disease (-5.3, 95% CI -8.2,-2.3; P < 0.001) and stroke risk (-4.4, 95% CI -7.5, -1.3; P < 0.001). CONCLUSION: Multifactorial intervention with structured diabetes self-management education compared with usual diabetes care has benefits for cardio-metabolic risk factor profile. There was no increase in severe hypoglycaemia and cardiovascular mortality despite intensive glycaemic control, although the study was not powered to assess these outcomes.

Ectopic prolactin secretion secondary to an ovarian tumour.

UNLABELLED: Ectopic hormone secretion is a well-recognised phenomenon; however, ectopic prolactin secretion is exceptionally rare. Hoffman and colleagues reported the first ever well-documented case of ectopic prolactin secretion secondary to a gonadoblastoma. We report a lady who presented with galactorrhoea and a large ovarian tumour that was found to secrete high levels of prolactin. LEARNING POINTS: Aim of this case report is to highlight the occurrence of this condition.Lack of awareness can often lead to a diagnostic conundrum.

Association of cardiac and non-cardiac chronic disease comorbidity on glycaemic control in a multi-ethnic population with type 1 and type 2 diabetes.

AIMS: To determine the prevalence of chronic disease comorbidity in south Asians (SAs) and white Europeans (WEs) with diabetes and to quantify the relationship of cardiac disease comorbidity (CDCM) and non-cardiac disease comorbidity (NCCM) to glycaemic control in SAs and WEs with type 1 and type 2 diabetes mellitus. METHODS: A cross-sectional study using a database of patients of SA (25.5%) and WE (74.5%) origin attending a specialist diabetes clinic in the UK between 2003 and 2005 (n=5664). RESULTS: The prevalence of SAs and WEs with type 1 diabetes was 12% and 88%, respectively; for those with type 2 diabetes the prevalence was 30% and 70%, respectively. Overall, the prevalence of comorbidity in people with type 1 diabetes was 25.5% and with type 2 diabetes was 47%. NCCM was more prevalent in WEs than SAs (17.6% vs 12.8%, p<0.001). In type 2 diabetes, the prevalence of suboptimal glycaemic control was significantly greater in SAs compared to WEs with NCCM and CDCM (79% vs 62%, p<0.001; 78% vs 65%, p<0.001, respectively). SAs with type 2 diabetes and comorbidity had excess odds of suboptimal glycaemic control compared to WEs: OR 2.27 (95% CI 1.50 to 3.43) for those with NCCM and OR 1.91 (95% CI 1.49 to 2.44) for those with CDCM. CONCLUSIONS: The prevalence of CDCM is higher in SAs compared to WEs with type 2 diabetes, whereas the prevalence of NCCM is higher in WEs compared to SAs. Taking into account comorbidities, SAs (compared to WEs) with type 2 diabetes had an excess risk of having HbA1c ≥7% ranging from 1.86- to 2.27-fold. Further research is needed to identify the reasons for unfavourable metabolic conditions in SAs and also develop and evaluate interventions.

Multifactorial intervention in individuals with type 2 diabetes and microalbuminuria: the Microalbuminuria Education and Medication Optimisation (MEMO) study.

AIMS: To determine whether tighter cardiovascular risk factor control with structured education in individuals with type 2 diabetes (T2DM) and microalbuminuria benefits cardiovascular risk factors. METHODS: Participants from a multiethnic population, recruited from primary care and specialist clinics were randomised to intensive intervention with structured patient (DESMOND model) education (n=94) or usual care by own health professional (n=95). PRIMARY OUTCOME: change in HbA1c at 18months. SECONDARY OUTCOMES: changes in blood pressure (BP), cholesterol, albuminuria, proportion reaching risk factor targets, modelled cardiovascular risk scores. RESULTS: Mean (SD) age and diabetes duration of participants were 61.5 (10.5) and 11.5 (9.3) years, respectively. At 18months, intensive intervention showed significant improvements in HbA1c (7.1(1.0) vs. 7.8(1.4)%, p<0.0001), systolic BP (129(16) vs. 139(17) mmHg, p<0.0001), diastolic BP (70(11) vs. 76(12) mmHg, p<0.001), total cholesterol (3.7(0.8) vs. 4.1(0.9) mmol/l, p=0.001). Moderate and severe hypoglycaemia was 11.2 vs. 29.0%; p=0.001 and 0 vs. 6.3%; p=0.07, respectively. More intensive participants achieved ≥3 risk factor targets with greater reductions in cardiovascular risk scores. CONCLUSIONS: Intensive intervention showed greater improvements in metabolic control and cardiovascular risk profile with lower rates of moderate and severe hypoglycaemia. Intensive glycaemic interventions should be underpinned by structured education promoting self-management in T2DM.

Insulin U-500 in severe insulin resistance in type 2 diabetes mellitus.

Some patients with type 2 diabetes mellitus (T2DM) are profoundly insulin resistant and require large insulin doses to achieve optimal glycaemic control. However, large volumes of subcutaneous conventional U-100 insulin can cause discomfort at the injection site, resulting in poor concordance with insulin therapy. One therapeutic option is the use of U-500 insulin, thus reducing the insulin volume by 80%. This review will address the practical issues associated with the use of U-500, clinical efficacy and safety aspects of this concentrated insulin, which has an important role in a subgroup of patients with T2DM.

A randomized controlled trial examining combinations of repaglinide, metformin and NPH insulin.

AIMS: To compare combination use of repaglinide, metformin and bedtime Neutral Protamine Hagedorn (NPH) insulin with conventional approaches of insulin initiation in patients with Type 2 diabetes (T2DM). METHODS: Eighty-two patients with T2DM with suboptimal glycaemic control on oral glucose-lowering agents were randomized to one of three treatment regimens for 4 months. Group 1 received metformin and twice daily biphasic 30/70 human insulin mixture (n = 27), group 2 metformin and bedtime NPH insulin (n = 26) and group 3 metformin, bedtime NPH insulin and mealtime repaglinide (n = 25). RESULTS: Seventy-five patients completed the study. Baseline and end-point mean HbA1c levels fell from 9.0 +/- 1.1 to 7.9 +/- 1.1% in group 1, 10.0 +/- 2.2 to 9.2 +/- 1.4% group 2 and 10.0 +/- 1.7 to 8.1 +/- 1.5% in group 3, respectively. All groups showed improvements in HbA1c. There was no significant difference between groups in the proportions of patients experiencing hypoglycaemia (29.6, 25.0 and 16.7%, respectively; P = 0.55) or in mean weight gain (2.9, 0.7 and 2.2 kg, respectively; P = 0.06). By 4 months, insulin doses were 0.63 +/- 0.32 IU/kg in group 1, 0.58 +/- 0.21 IU/kg in group 2 and 0.37 +/- 0.22 IU/kg in group 3 (group 3 vs. groups 1 and 2: P < 0.002). CONCLUSIONS: The approach using repaglinide, metformin and NPH insulin improved glycaemic control with a similar safety profile to conventional insulin initiation in T2DM and produced final glycaemic control similar to metformin and a twice daily biphasic insulin mixture.

U-500 insulin: why, when and how to use in clinical practice.

Some patients with type 2 diabetes mellitus (T2DM) have severe insulin resistance. Their insulin requirements are significantly greater. These patients need to take 2-3 injections at the same time to take the correct insulin dose or to redial the insulin pen. When daily insulin requirements are in excess of 300 units/day, the volume of the injected insulin becomes an issue. Large-volume injection can cause discomfort and lead to poor concordance with treatment. Using high-strength insulin e.g. U-500 insulin can reduce the volume of the injected insulin. Despite publications of small case reports or case series, no universal guidelines exist on the use of U-500 insulin. We discuss common sense approaches when considering the use of U-500 insulin in clinical practice.

Glargine versus NPH insulin: efficacy in comparison with insulin aspart in a basal bolus regimen in type 1 diabetes--the glargine and aspart study (GLASS) a randomised cross-over study.

The aim of the study was to compare the efficacy of insulin glargine and aspart with NPH insulin and aspart in a basal bolus regimen in type 1 diabetes. In this 36-week randomised open-label two-period cross-over trial, subjects received 16 weeks' treatment with either once-daily insulin glargine or twice-daily NPH insulin after 4-week run-in. Primary outcome was HbA1c and secondary outcomes were fasting plasma glucose (FPG), weight change, incidence of hypoglycaemia, effect on lipid profile and patient satisfaction. Sixty patients with type 1 diabetes were recruited (33 male, mean age 42.7 years, mean HbA1c 8.53%) with 53 completing the study. At completion, HbA1c was lower with glargine and aspart than with NPH and aspart (8.07% versus 8.26%, difference -0.19 [95% CI 0.37-0.01]%, p=0.04). FPG was significantly different between glargine and NPH (p=0.002), with mean FPG on glargine 3mmol/L lower than on NPH at the end of the study. There were no differences in hypoglycaemia rate (p=0.63), weight (p=0.45) or lipid profile (p=0.18). Patient satisfaction was greater with glargine (DTSQ, p=0.001). Three patients discontinued as they wished to remain on glargine. We suggest that glargine combined with aspart is an effective basal bolus regimen in type 1 diabetes.

Metabolic alkalosis and myoclonus.

This is the first case reported of vomiting-induced metabolic alkalosis associated with myoclonus. The report describes an unusual presentation of myoclonus secondary to acid-base disturbance caused by recreational drug-induced vomiting. The severe derangement of hyponatraemia, hypokalaemia, and alkalosis appears to have been reasonably well tolerated due to the gradual onset and relatively long history. The causes, mechanism, and management of metabolic alkalosis are discussed.

Comparative incidence of Type I diabetes in children aged under 15 years from South Asian and White or Other ethnic backgrounds in Leicestershire, UK, 1989 to 1998.

AIMS/HYPOTHESIS: Estimates of incidence of Type I (insulin-dependent) diabetes mellitus in childhood populations vary around the world. This study aimed to estimate and compare the incidence of Type I diabetes in Leicestershire of children of South Asian and White or Other ethnic backgrounds. METHODS: All new cases of childhood-onset Type I diabetes diagnosed before 15 years of age in Leicestershire during the period 1989-98 were studied. Population data for Leicestershire from the 1991 census was used. Ethnicity was assigned to all children in the study according to their surnames. Incidence rates (95%-Confidence limits) for the South Asian and white or other ethnic group were estimated and compared. RESULTS: Over the 10-year period, 46 South Asian children and 263 children who were white or from another ethnic group fulfilled the criteria for inclusion in the study. Crude incidence rates per 100,000 person-years were 19.2 (12.0, 29.1) girls and 20.3 (13.0, 30.3) boys for South Asians and 17.7 (14.8, 21.1) girls and 17.7 (14.8, 20.9) boys for whites/others. Age and sex-specific rates were higher for South Asians over 5 years of age but differences were not statistically significant. CONCLUSION/INTERPRETATION: Type I diabetes incidence rates for South Asian children in Leicestershire were very similar to those for children who were in the white/other ethnic group, in contrast to very low rates reported from Asia. The convergence of rates for South Asians with other ethnic groups in Leicestershire suggests that environmental factors are more important than genetic predisposition in causing Type I diabetes in people of South Asian ethnic background.

Inequalities in access to diabetes care: evidence from a historical cohort study.

OBJECTIVE: To establish which factors predict attendance at a hospital diabetes clinic and for diabetes review in general practice. DESIGN: A historical cohort study of individuals with diabetes identified from general practice records. Information on service contacts and other clinical, social, and demographic variables was collected from general practice records and postal questionnaires. SETTING: Seven Leicestershire general practices. SUBJECTS: Individuals registered with study practices who had a diagnosis of diabetes made before 1990. MAIN OUTCOME MEASUREMENTS: Attendance at a hospital diabetes clinic or for a documented diabetes review in general practice at least once between 1990 and 1995. RESULTS: 124 (20%) had at least one recorded diabetes review in general practice and 332 (54%) attended a hospital diabetes clinic at least once. The main predictors of attending a hospital clinic were younger age, longer duration of diabetes, and treatment with insulin. Access to a car (OR 1.34, 95% CI 1.06 to 1.71), home ownership (OR 1.48, 95% CI 1.14 to 1.58) and a non-manual occupation (OR 1.56, 95% CI 1.09 to 2.24) were all associated with an increased likelihood of attending, although living in a less deprived area was not. The main predictors of attending for review in general practice were older age, less co-morbidity, and being white. Living in a more deprived area was related to a reduced chance of review in general practice (OR 0.81, 95% CI 0.76 to 0.86) while individual socioeconomic indicators were not. CONCLUSIONS: Whilst an indicator of area deprivation predicts reduced likelihood of review in general practice, individual indicators predict reduced likelihood of attending outpatients. This suggests a need for different approaches to tackling inequalities in access to care in primary and secondary care settings.

Do diabetes clinic attendees stay out of hospital? A matched case-control study.

AIMS: To examine whether routine care for diabetes mellitus influences the risk of hospital admission. METHODS: All people with diabetes in five randomly selected general practices in the city of Leicester were identified from medical records and prescribing information. Cases with a hospital admission between 1992 and 1995 but no admission in the preceding 2 years were compared with age-matched controls in a nested study. RESULTS: The variables significantly associated with an increased risk of admission were duration of diabetes in years (OR 1.07, 95% confidence interval (CI) 1.03-1.11) and number of non-diabetic drugs prescribed (OR 1.51, 95% CI 1.27-1.79). Having attended a hospital clinic in the previous 2 years was associated with reduced risk of admission (OR 0.30, 95% CI 0.14-0.65), whilst having been seen for a diabetes review in general practice was not (OR 0.91, 95% CI 0.41-1.99). Similar results were found for both diabetes-related and unrelated admissions. CONCLUSIONS: Although general practice-based review was not associated with a change in the risk of admission, attendance at a hospital clinic was associated with a decreased risk of admission. These results may be explained by the characteristics of those who attend hospital clinics, as well as by the possible effectiveness of access to specialist services in reducing admissions.

Potential impact of a change in the diagnostic criteria for diabetes mellitus on the prevalence of abnormal glucose tolerance in a local community at risk of diabetes: impact of new diagnostic criteria for diabetes mellitus.

AIMS: To compare the prevalence of diabetes and abnormal glucose metabolism using conventional and suggested new WHO and new ADA criteria in a group of people with symptoms of diabetes. METHODS: We examined retrospectively the results of 154 consecutive OGTTs in such patients performed using capillary whole blood. RESULTS: With the 1985 WHO criteria. Forty-four point eight per cent of subjects (69 subjects, with 95% confidence intervals, 37-52.6%) had diabetes, 47.8% (33 subjects, 36-59.6%) had a normal fasting glucose, 31.2% (48 subjects, 23.9-38.5%) had impaired glucose tolerance (IGT) and 76% (117 subjects, 69.3-82.7%) had abnormal glucose tolerance. Applying the ADA criteria (fasting capillary whole blood only), 33.1% (51 subjects, 25.7-40.5%) had diabetes (a 26% relative reduction) and 11% (17 subjects, 6.1-15.9%) IFG, with 44.1% (68 subjects, 36.3-51.9%) having abnormal glucose metabolism (a 42% relative reduction). If the proposed 1998 WHO criteria were used, the number with diabetes increase to 48% (74 subjects, 40.1-55.9%) a 7.2% increase on the old criteria. 27.9% (43 subjects, 20.8-35%) had IGT, so the number with some degree of abnormal glucose metabolism remains unchanged. Use of the ADA criteria, considering only the fasting glucose as suggested, will result in a significant reduction in the diagnosis of diabetes and those with abnormal glucose metabolism.

A defect in the regional deposition of adipose tissue (partial lipodystrophy) is encoded by a gene at chromosome 1q.

Partial lipodystrophy (PLD), also known as "Dunnigan-Kobberling syndrome," is transmitted as a highly penetrant autosomal dominant disorder that is characterized by a dramatic absence of adipose tissue in the limbs and trunk, more evident in females than in males. In contrast, fat is retained on the face, in retro-orbital space, and at periserous sites. Associated metabolic abnormalities, including insulin resistance, hyperinsulinemia, and dyslipidemia, are referred to as "metabolic syndrome X" (Reaven 1988). Despite the intense interest in the genetic determinants underlying fat deposition, the genes involved in the lipodystrophic syndromes have not been identified. We ascertained two multigeneration families, with a combined total of 18 individuals with PLD, and performed a genomewide search. We obtained conclusive evidence for linkage of the PLD locus to microsatellite markers on chromosome 1q21 (D1S498, maximum LOD score 6.89 at recombination fraction .00), with no evidence of heterogeneity. Haplotype and multipoint analysis support the location of the PLD locus within a 21.2-cM chromosomal region that is flanked by the markers D1S2881 and D1S484. These data represent an important step in the effort to isolate and characterize the PLD gene. The identification of the gene will have important implications for the understanding of both developmental and metabolic aspects of the adipocyte and may prove useful as a single-gene model for the common metabolic disorder known as "syndrome X."

Evidence of defective cardiovascular regulation in insulin-dependent diabetic patients without clinical autonomic dysfunction.

(1) Autonomic dysfunction is a well recognised complication of diabetes mellitus and early detection may allow therapeutic manoeuvres to reduce the associated mortality and morbidity. We sought to identify early cardiovascular autonomic neuropathy using spectral analysis of heart rate and systolic blood pressure variability. (2) Thirty patients with Type 1 (insulin-dependent) diabetes mellitus (DM) and 30 matched control subjects were studied. In addition to standard tests of autonomic function, heart rate and systolic blood pressure variability were assessed using power spectral analysis. From the frequency domain analysis of systolic blood pressure and R-R interval, the overall gain of baroreflex mechanisms was assessed. (3) Standard tests of autonomic function were normal in both groups. Total spectral power of R-R interval was reduced in the Type 1 DM group for low-frequency (473 +/- 63 vs. 747 +/- 78 ms2, mean +/- S.E.M., P = 0.002) and high-frequency bands (125 +/- 13 vs. 459+/-90 ms2, P < 0.0001). Systolic blood pressure low-frequency power was increased in the diabetic group (9.3 +/- 1.2 vs. 6.6+/-0.7 mmHg2, P < 0.05). The low frequency/high frequency ratio for heart rate variability was significantly higher in the Type 1 DM patients (4.6+/-0.5 vs. 2.9+/-0.5, P = 0.002), implying a relative sympathetic predominance. When absolute powers were expressed in normalised units, these differences persisted. There were significant reductions in baroreceptor-cardiac reflex sensitivity in Type 1 DM patients compared to controls while supine (9.7+/-0.7 vs. 18.5 +/- 1.7 ms/mmHg, P < 0.0001) and standing (2.9+/-0.9 vs. 7.18+/-1.9 ms/mmHg, P < 0.001). (4) Spectral analysis of cardiovascular variability detects autonomic dysfunction more frequently in Type 1 DM patients than conventional tests, and is suggestive of an abnormality of parasympathetic function. The abnormality of baroreceptor-cardiac reflex sensitivity could be explained by this impairment of parasympathetic function and this may predispose to the development of hypertension and increase the risk of sudden cardiac death. Using spectral analysis methods may allow detection of early diabetic cardiac autonomic neuropathy and allow therapeutic intervention to slow the progression.

Increased epidermal growth factor in experimental diabetes related kidney growth in rats.

Renal enlargement is a characteristic feature of human and experimental diabetes mellitus that may be predictive of subsequent nephropathy. In the streptozotocin diabetic rat kidney growth rapidly follows the induction of experimental diabetes but the mechanisms responsible for this growth are poorly understood. Epidermal growth factor (EGF) is a potent mitogen for renal tubular cells. Thirty one male Sprague-Dawley rats aged 13 weeks were randomised to receive either streptozotocin (diabetic, n = 20) or buffer (control, n = 11). Animals were studied on days 1, 3, 5 and 7 following streptozotocin. Diabetes was associated with a 3-fold increase in urinary EGF excretion (223 +/- 15 vs 59 +/- 5 ng/day, mean +/- SEM, diabetic vs control, p < 0.0001) and 3-6 fold increase in renal EGF mRNA relative to controls (p < 0.001). A transient rise in kidney EGF protein was noted on day 1. There was no difference between diabetic and control animals with regard to intrarenal sites of EGF expression or in plasma EGF. These data suggest that the increased urinary EGF excretion in diabetic animals is the result of enhanced local production and that EGF is not stored for a prolonged period within renal tubular cells but is released following its synthesis. In the context of the known intrarenal actions of EGF this growth factor may play a role in the pathogenesis of diabetes related kidney growth.

Can abnormalities of ventricular repolarisation identify insulin dependent diabetic patients at risk of sudden cardiac death?

OBJECTIVE: To study the possible association or QT dispersion and mean QTc intervals, as measured from standard 12 lead electrocardiograms, with baroreceptor-cardiac reflex sensitivity (BRS) in insulin dependent diabetic patients. DESIGN: Comparative study of non-invasive assessment of BRS, QT interval, and QT dispersion. SETTING: Large teaching hospital. SUBJECTS: 31 young asymptomatic, normotensive, insulin dependent diabetic patients, aged 20-55 years with normal clinical autonomic function. METHODS: QT intervals and QT dispersion were measured by a single observer blinded to other data about the patients. BRS was measured after activating the baroreflex with a Valsalva manoeuvre, and the rate in change of R-R interval to increasing systolic pressure during phase 4 was measured; in addition sequence analysis of resting systolic blood pressure and heart rate was performed during standing. The alpha coefficient--an index of the overall gain of the baroreflex mechanisms--was estimated from spectral analysis data of systolic blood pressure and pulse interval variability. RESULTS: Mean (SD) QTc interval was 406 (23) ms, QT dispersion was 44 (13) ms. There was no association between QT dispersion and any measurement of BRS. There was a negative correlation between mean QTc intervals and sequence analysis BRS (r = -0.355, P = 0.049), but no association with Valsalva BRS. The alpha coefficient, showed a significant negative correlation with mean QTc (r = -0.42, P = 0.008). CONCLUSIONS: Abnormal BRS may be reflected in the heart by global prolongation of ventricular repolarisation, but not by dispersion of ventricular repolarisation. This may, in part, explain the increase in sudden cardiac death seen in IDDM patients.

Is impaired baroreflex sensitivity a predictor or cause of sudden death in insulin-dependent diabetes mellitus?

Sudden death at night is known to occur in young patients with insulin-dependent (Type 1) diabetes mellitus (IDDM) but the aetiology is uncertain. A cardiac arrhythmia has been postulated, but there has been little evidence to support this. We present the case of a 31-year-old man with IDDM of 17 years duration, who died suddenly while asleep. Over preceding months, he had had strict glycaemic control (HbA1 8.9%), normal 24 h blood pressure (mean 131 +/- 2.1/76 +/- 2.2 mmHg), no evidence of microangiopathy or endothelial dysfunction and normal standard clinical tests of autonomic function. An electrocardiogram was similarly unremarkable, with a QTc interval of 0.414 s, and an echocardiogram had demonstrated normal left ventricular mass index (96.4 g m-2). However, there was no nocturnal dip in heart rate (daytime 74 +/- 2.7, and nocturnal 68 +/- 1.6 beats min-1), and he had grossly impaired baroreflex sensitivity during Phase 4 of the valsalva manoeuvre (0.5 ms mmHg-1), with power spectral analysis studies suggesting an abnormality of parasympathetic function. The coroner's autopsy demonstrated no structural abnormalities. We hypothesize that abnormal baroreflex sensitivity could either predict a risk of or account for some of the unexplained deaths in IDDM, in that relative overactivity of the sympathetic nervous system could cause ventricular arrhythmias.