Hand disorders, hand function, and activities of daily living in elderly men with type 2 diabetes.

AIMS/HYPOTHESIS: This study aimed to examine hand disorders, symptoms, overall hand function, activities of daily living (ADLs), and life satisfaction in elderly men with type 2 diabetes mellitus (DM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). METHODS: Subjects were interviewed and evaluated with a battery of clinical and laboratory tests, including hand assessment, and a questionnaire. RESULTS: HbA1c differed between groups (highest in DM, especially in long-term DM). Limited joint motion (LJM), for example, prayer sign and Dupuytren's contracture, was most common in individuals with DM, followed by individuals with IGT, as compared to those with NGT. Vibrotactile sense was impaired symmetrically in the index and little fingers in DM. However, there were no differences for sensibility, dexterity, grip strength, and cold intolerance between groups. Individuals with long-term (>15 years) DM were more affected regarding sensibility and ADL than individuals with short-term DM, who had more sleep disturbances. ADL difficulties were less among IGT subjects. Vibrotactile sense showed correlations with Semmes-Weinstein monofilament test and static two-point discrimination. CONCLUSIONS/INTERPRETATION: Dupuytren's contracture and impaired vibrotactile sense in finger pulps occurred in patients with DM but not in those with IGT, although LJM occurred in both IGT and DM patients. A longer duration of DM was associated with more severe neuropathy and ADL difficulties. Life satisfaction was high, and hand disorders did not have a significant impact on ADL.

Maternal enterovirus infection during pregnancy as a risk factor in offspring diagnosed with type 1 diabetes between 15 and 30 years of age.

Maternal enterovirus infections during pregnancy may increase the risk of offspring developing type 1 diabetes during childhood. The aim of this study was to investigate whether gestational enterovirus infections increase the offspring's risk of type 1 diabetes later in life. Serum samples from 30 mothers without diabetes whose offspring developed type 1 diabetes between 15 and 25 years of age were analyzed for enterovirus-specific immunoglobulin M (IgM) antibodies and enterovirus genome (RNA), and compared to a control group. Among the index mothers, 9/30 (30%) were enterovirus IgM-positive, and none was positive for enterovirus RNA. In the control group, 14/90 (16%) were enterovirus IgM-positive, and 4/90 (4%) were positive for enterovirus RNA (n.s.). Boys of enterovirus IgM-positive mothers had approximately 5 times greater risk of developing diabetes (OR 4.63; 95% CI 1.22-17.6), as compared to boys of IgM-negative mothers (P < .025). These results suggest that gestational enterovirus infections may be related to the risk of offspring developing type 1 diabetes in adolescence and young adulthood.

Sympathetic nerve dysfunction is common in patients with chronic intestinal pseudo-obstruction.

GOAL: To clarify whether disturbances in the autonomic nervous system, reflected in abnormal cardiovascular reflexes, could explain symptoms of impaired heat regulation in patients with intestinal pseudo-obstruction. BACKGROUND: Chronic intestinal pseudo-obstruction is a clinical syndrome characterized by diffuse, unspecific gastrointestinal symptoms due to damage to the enteric nervous system or the smooth muscle cells. These patients often complain of excessive sweating or feeling cold, suggesting disturbances in the autonomic nervous system. Earlier studies have pointed to a coexistence of autonomic disturbances in the enteric and cardiovascular nervous system. STUDY: Thirteen consecutive patients (age range 23 to 79, mean 44 y) fulfilling the criteria for chronic intestinal pseudo-obstruction were investigated. Six of them complained of sweating or a feeling of cold. Examination of autonomic reflexes included heart rate variation to deep-breathing (expiration/inspiration index), heart rate reaction to tilt (acceleration index, brake index), and vasoconstriction (VAC) due to indirect cooling by laser doppler (VAC-index; high index indicates impaired VAC). Test results in patients were compared with healthy individuals. RESULTS: Patients had significantly higher (more abnormal) median VAC-index compared with healthy controls [1.79 (interquartile ranges 1.89) vs. 0.08 (interquartile ranges 1.29); P=0.0007]. However, symptoms of impaired heat regulation were not related to the VAC-index. There were no differences in expiration/inspiration, acceleration index, or brake index between patients and controls. CONCLUSIONS: The patients with severe gastrointestinal dysmotility showed impaired sympathetic nerve function which, however, did not seem to be associated with symptoms of impaired heat regulation.

Number of islet autoantibodies present in newly diagnosed type 1 diabetes children born to non-diabetic mothers is affected by islet autoantibodies present at birth.

OBJECTIVE: Cord blood islet autoantibodies in children born to mothers with type 1 diabetes may be associated with a reduced risk of islet autoimmunity and diabetes. The aim of this study was to investigate in children with type 1 diabetes but born to non-diabetic mothers whether islet autoantibodies at birth affected their presence at diagnosis. PATIENTS AND METHODS: Serum samples at birth and at diagnosis were available from 141 children who developed type 1 diabetes between 1 and 19 yr of age (median 9.0 yr; male/female ratio 83/58). The samples were tested for autoantibodies against glutamic acid decarboxylase, insulinoma-associated antigen 2, and insulin as well as for islet cell antibodies. The human leukocyte antigen genotype was also determined. RESULTS: The frequency of islet autoantibodies in the umbilical cord blood was 11% compared with 91% at diagnosis. Children with fewer islet autoantibodies at diagnosis were more likely to have had autoantibodies at birth (p = 0.02). Autoantibodies present in cord blood at birth were observed in 25% (3/12) of children with no islet autoantibodies at diagnosis, in 17% (7/42) of children with one or two antibodies at diagnosis, and in only 5% (4/86) of children with more than two antibodies, demonstrating an inverse relationship between autoantibodies at birth and at diagnosis (test for trend, p < 0.001). CONCLUSIONS: Our preliminary data suggest that exposure to cord blood islet autoantibodies may influence the presence of islet autoantibodies at the time of diagnosis of type 1 diabetes and explain why some type 1 diabetes children are islet autoantibody negative at clinical diagnosis.

Subclinical sympathetic neuropathy appears early in the course of Crohn's disease.

BACKGROUND: We have previously demonstrated that patients with Crohn's disease (CD) of long duration have signs of autonomic neuropathy. The aim of this study was to examine whether autonomic neuropathy is an early manifestation of CD, or a sign appearing late in the course. METHODS: Twenty patients, median age 40 years, with a short duration of CD were included. Examination of autonomic reflexes included heart rate reaction to tilt (acceleration index - AI, brake index - BI) and heart rate variation to deep-breathing (expiration/inspiration index-E/I). Seven years later the same examinations were repeated, and in addition we examined the vasoconstriction response to indirect cooling by laser Doppler (vasoconstriction-index - VAC-index). The results were compared with healthy individuals. RESULTS: There was no difference in the blood pressure between controls and the patients with CD at rest, but eight minutes after tilt, the systolic blood pressure was lowered in patients compared to controls, both at the first assessment (p = 0.016) and after seven years (p = 0.042). The change in systolic blood pressure between rest and eight minutes after tilt was not significant at the first assessment, while a significant change compared to controls was observed seven years later (p = 0.028). This indicates a progressive dysfunction. There were no differences in E/I, AI, BI or VAC indexes between patients and controls. CONCLUSION: Patients with CD suffer from autonomic neuropathy early in their disease, suggesting involvement of many different organ systems in this entity.

Early changes in glomerular size selectivity in young adults with type 1 diabetes and retinopathy. Results from the Diabetes Incidence Study in Sweden.

OBJECTIVE: To investigate the relationship between early-onset retinopathy and urinary markers of renal dysfunction. RESEARCH DESIGN AND METHODS: The Diabetes Incidence Study in Sweden (DISS) aims to register all new cases of diabetes in young adults (15-34 years). In 1987-1988, 806 patients were reported and later invited to participate in a follow-up study focusing on microvascular complications after approximately 10 years of diabetes. In the present study, 149 patients with type 1 diabetes, completed eye examination, and urine sampling were included. RESULTS: The patients with retinopathy (n=58, 39%) had higher HbA(1c) (P<.001) and urinary IgG2/creatinine (P<.05) and IgG2/IgG4 ratios (P<.05). Patients with maculopathy had the highest levels. No significant differences in urinary albumin/creatinine, glycosaminoglycans (GAGs)/creatinine, Tamm-Horsfall protein (THP)/creatinine, and IgG4/creatinine ratios were found. Women had higher urinary albumin/creatinine (P<.01) and urinary IgG2/creatinine ratios (P<.01) than men. CONCLUSIONS: Young adults with type 1 diabetes and early-onset retinopathy had higher IgG2/creatinine and IgG2/IgG4 ratios than patients without retinopathy indicating that retinopathy is associated with a change in glomerular size selectivity. This was found in association with normal urinary albumin and THP excretion and may be suspected to reflect early general vascular changes.

Enteric ganglioneuritis and abnormal interstitial cells of Cajal: features of inflammatory bowel disease.

BACKGROUND: An increased prevalence of irritable bowel syndrome (IBS) and disturbances in cardiac and blood pressure reflexes have been described in patients with Crohn's disease (CD) and ulcerative colitis (UC). These features could be due to abnormalities in the gastrointestinal neurotransmission. The aims of this study were to examine whether histopathologic changes in the enteric nervous system correlate with disturbances in cardiac and blood pressure reflexes and the occurrence of IBS- and dyspepsia-like symptoms in these patients. METHODS: Thirty patients with CD and UC with bowel resection were examined by deep-breathing and orthostatic tests. The resection specimens were evaluated histologically regarding visceral neuro- or myopathy. All medical records were studied for treatment and clinical course. RESULTS: Ganglioneuritis was observed in 11 of 19 patients with CD and in 5 of 11 with UC. Only patients with CD had ganglioneuritis in the small intestine. Moreover, in CD the interstitial cells of Cajal (ICCs) in the small bowel showed atrophy and vacuolar degeneration, along with a reduced number of cells (P = 0.005). In UC the colonic ICCs were hyperplastic (P = 0.05) without signs of degeneration. The indices of deep-breathing and orthostatic tests were impaired, except in CD with ganglioneuritis, who showed normal test values. There were no correlations between histopathologic alterations versus IBS and dyspepsia. CONCLUSIONS: Visceral ganglioneuritis and pathologic ICCs were observed in patients with CD and UC. However, these histopathologic abnormalities could not be related to the clinical or autonomic features of the disease.

Decreased heart rate variability may predict the progression of carotid atherosclerosis in type 2 diabetes.

Heart rate variability (HRV), a measure of autonomic function, can predict survival outcomes. Cardiovascular disease is a known complication of diabetes, and we aimed to determine if autonomic dysfunction was associated with carotid artery atherosclerotic plaques in type 2 diabetic patients. We assessed frequency domain HRV from power spectral analysis of 24 h Holter ECG recordings, expiration/inspiration (E/I) ratio during deep breathing, acceleration index (AI) of R-R interval in response to head-up tilt, and the degree of carotid artery atherosclerosis in 61 type-2 diabetic patients (39 males, 45-69 years). Studies were carried out 5-6 years after diagnosis (baseline) and repeated 8 years after diagnosis (follow-up). At baseline, patients diagnosed with autonomic neuropathy, with abnormal E/I ratio and abnormal AI measurements, had decreased low frequency (LF) HRV. Baseline E/I ratio correlated with day (r = 0.34; P < 0.001) and night-time (r = 0.44; P < 0.001) LF power. Night-time HRV did not differ in patient with and without autonomic neuropathy. Reduced common carotid artery diameter and atherosclerotic intima-media thickness (IMT) both correlated with HRV at baseline. At follow-up, all HRV variables decreased significantly. Furthermore, patients with lower LF power at baseline, had a larger increase in the thickness of the carotid bulb intima-media at follow-up. Our results show that LF HRV power is associated with the extent and progression of carotid atherosclerosis in type 2 diabetes. A low LF HRV may predict the progression of atherosclerosis in these patients.

The influence of wavelength and probe configuration on findings of a skin vasoconstriction test when using laser Doppler perfusion devices.

The aim of this study was to establish the degree to which a standardized test based on laser Doppler blood flow measurement is dependent on the particular equipment set-up being used. For this purpose, we examined finger skin blood flow with laser Doppler instruments in 20 healthy subjects. In laser Doppler perfusion monitoring (LDPM), we used a custom-made probe with two detecting fibers placed 0.25 and 1.2 mm from the illuminating fiber, respectively, and two laser Doppler perfusion imagers (LDPI) with a wavelength of 632.8 nm and 780 nm, respectively. Warming of the hand was achieved with a Peltier element, and reflex vasoconstriction was induced by immersing the other hand for 3 min into a water bath kept at 15 degrees C. As a measure for the change in skin blood flow, a vasoconstriction index (VAC: cooling/before cooling) was calculated and used for the comparison of the different devices. VAC values gathered around 0.6 for all devices. However, LDPI with a wavelength of 632.8 nm showed a slightly higher VAC index, and the difference was significant. We conclude that using a standardized test is the most appropriate for monitoring changes in blood flow rather than recording and comparing discrete values in intermittent recordings. Although a difference was noted when comparing the devices, different fiber separations and wavelengths seem then to be of little consequence.

Latent autoimmune diabetes in adults: definition, prevalence, beta-cell function, and treatment.

Latent autoimmune diabetes in adults (LADA) is a disorder in which, despite the presence of islet antibodies at diagnosis of diabetes, the progression of autoimmune beta-cell failure is slow. LADA patients are therefore not insulin requiring, at least during the first 6 months after diagnosis of diabetes. Among patients with phenotypic type 2 diabetes, LADA occurs in 10% of individuals older than 35 years and in 25% below that age. Prospective studies of beta-cell function show that LADA patients with multiple islet antibodies develop beta-cell failure within 5 years, whereas those with only GAD antibodies (GADAs) or only islet cell antibodies (ICAs) mostly develop beta-cell failure after 5 years. Even though it may take up to 12 years until beta-cell failure occurs in some patients, impairments in the beta-cell response to intravenous glucose and glucagon can be detected at diagnosis of diabetes. Consequently, LADA is not a latent disease; therefore, autoimmune diabetes in adults with slowly progressive beta-cell failure might be a more adequate concept. In agreement with proved impaired beta-cell function at diagnosis of diabetes, insulin is the treatment of choice.

Autoantibodies to autonomic nerves associated with cardiac and peripheral autonomic neuropathy.

OBJECTIVE: This study examines whether autonomic nerve autoantibodies (ANabs) are associated with development of autonomic neuropathy using a prospective study design. RESEARCH DESIGN AND METHODS: A group of type 1 diabetic patients were followed prospectively with regard to autonomic nerve function on four occasions. At the third examination, 41 patients were tested for ANabs (complement-fixing autoantibodies to the sympathetic ganglion, vagus nerve, and adrenal medulla), and the results were related to cardiac autonomic nerve function (heart rate variation during deep breathing [expiration/inspiration ratio] and heart-rate reaction to tilt [acceleration and brake index]) and to peripheral sympathetic nerve function (vasoconstriction after indirect cooling [vasoconstriction index]). RESULTS: ANabs were detected in 23 of 41 (56%) patients at the third examination. Compared with patients without ANabs (ANabs-), patients with ANabs (ANabs+) showed significantly higher frequencies of at least one abnormal cardiac autonomic nerve function test at the third examination (17 of 23 [74%] vs. 7 of 18 [39%]; P = 0.03) and fourth examination (15 of 21 [71%] vs. 4 of 16 [25%]; P < 0.01). In contrast, there was no similar difference at the first or second examination. The relative risk for ANabs(+) patients to develop cardiac autonomic neuropathy at follow-up was 7.5 (95% CI 1.72-32.80). The vasoconstriction index was more abnormal in ANabs+ than in ANabs- patients at the fourth examination (median 1.40 [interquartile range 1.58] vs. 0.35 [2.05]; P = 0.01). CONCLUSIONS: ANabs were associated with future development of cardiac and peripheral autonomic neuropathy in diabetic patients, implying an etiological relationship between nervous tissue autoimmunity and these diabetes complications.

Changing associations between progressive cardiovascular autonomic neuropathy and carotid atherosclerosis with increasing duration of type 2 diabetes mellitus.

To clarify associations between cardiovascular autonomic neuropathy (CAN) and the progression of carotid artery atherosclerosis in Type 2 diabetic patients, cardiovascular autonomic nerve function was related to carotid artery ultrasound in 61 Type 2 diabetic patients, 5 and 8 years after the diagnosis of diabetes. Between 5 and 8 years after diagnosis, age-adjusted acceleration index (AI) decreased (from -0.306+/-1.034 to -0.702+/-1.072; P=.0139), whereas age-adjusted expiration/inspiration (E/I) ratio was unchanged (-0.583+/-1.038 and -0.828+/-1.028; P=.1164). Intima-media thickness (IMT) increased in both the common carotid artery (CCA; from 0.854+/-0.219 to 0.913+/-0.241 mm; P<.0001) and the carotid bulb (from 1.789+/-0.714 to 2.128+/-0.881 mm; P<.0001), corresponding to a yearly IMT increase of 0.032+/-0.039 mm in the CCA and 0.146+/-0.204 mm in the carotid bulb. This value did not correlate with the AI or E/I ratios. In age-controlled partial correlation in the first examination, AI correlated inversely with mean (r=-.33, P=.018) IMT in the CCA, but not with IMT in the carotid bulb (r=-.14, P=.303). However, in contrast to the first examination, at follow-up, AI correlated inversely with the mean IMT of the carotid bulb (r=-.40, P=.007), lumen diameter of the CCA (r=-.31, P=.034), and plaque score (r=-.29, P=.041), but not with IMT of the CCA (r=-.04, P=.861). There were no correlations between the E/I ratio and carotid variables. In conclusion, CAN was associated with features of carotid atherosclerosis, which, in the carotid bulb, might affect baroreceptor function with the progression of Type 2 diabetes.

Sympathetic and parasympathetic neuropathy are frequent in both type 1 and type 2 diabetic patients.

OBJECTIVE: The aim of this study was to evaluate the frequency of sympathetic versus parasympathetic neuropathy among type 1 and type 2 diabetic patients. RESEARCH DESIGN AND METHODS: There were 43 patients with type 1 and 17 with type 2 diabetes who were investigated. Sympathetic nerve function was assessed by measurement of the vasoconstriction (VAC) index by laser Doppler perfusion imaging of a locally heated finger followed by indirect cooling. Parasympathetic nerve function was assessed by R-R interval variation during deep breathing as measured by the expiration/inspiration (E/I) ratio. Results were expressed as age-corrected z scores in SD; VAC index >1.64 SD and E/I ratio <-1.64 SD were considered abnormal. RESULTS: VAC index was abnormal in 40% with type 1 and 41% with type 2 diabetes, whereas the E/I ratio was abnormal in 42% with type 1 and 65% with type 2 diabetes. There was a clear association between VAC index and E/I ratio among type 1 (rs=0.525; P=0.0002) but not among type 2 (rs=0.10) diabetic patients. Among type 2 diabetic patients, the degree of dysfunction was most severe regarding parasympathetic function (P=0.0167). CONCLUSIONS: Sympathetic and parasympathetic neuropathy were frequent in both type 1 and type 2 diabetic patients. However, there was a difference between the two types of diabetes. Sympathetic and parasympathetic nerve functions correlated in type 1 but not in type 2 diabetic patients. The explanation for this discrepancy might be that parasympathetic nerve function was most severely affected among type 2 diabetic patients.

CRP and IL-6 concentrations are associated with poor glycemic control despite preserved beta-cell function during the first year after diagnosis of type 1 diabetes.

BACKGROUND: The role of non-specific inflammation in beta-cell loss in type 1 diabetes is unclear. In the present study, inflammatory markers were determined in patients with newly diagnosed disease and related to beta-cell function, glycemic control and autoimmunity. METHODS: Ninety-seven adult patients with type 1 diabetes mellitus (80% islet antibody positives, ab(+)) were examined at diagnosis and 3, 6, 9 and 12 months after the start of insulin treatment. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, islet autoantibodies, insulin requirement and HbA(1c) were assessed. RESULTS: The concentrations of CRP were high-normal at diagnosis and did not change during the study period. A positive correlation between CRP at diagnosis and BMI was observed in ab(+) as well as in ab(-) cases. Detectable concentrations of IL-6 were found in 32% (157/485) of the samples and did not change during the study. Ab(-) patients had higher values of CRP at diagnosis and throughout the study compared to the ab(+). Among the ab(+) patients, CRP concentrations during the study were positively correlated to C-peptide at 12 months and an increase in HbA(1c) levels between 6 and 12 months. No associations between the presence or levels of islet autoantibodies and CRP were noted. CONCLUSIONS: In type 1 diabetes, the islet destructive process and the development of beta-cell remission are not associated with changes in CRP or IL-6. Instead, elevated CRP concentrations are prevalent and seem to reflect insulin resistance, as positive associations to BMI, C-peptide and deterioration of glycemic control were observed.

Laser Doppler perfusion monitoring of skin blood flow at different depths in finger and arm upon local heating.

The purpose of the study was to elucidate the vasodilatory response to local heating of the skin at two depths in two locations. To accomplish this, we measured skin blood flow in 12 healthy subjects using laser Doppler perfusion monitoring. A probe with two fibers separated 0.14 mm (superficial) and 0.25 mm (deeper) from the illuminating fiber was first attached to the distal phalanx of the index finger and thereafter to the dorsal forearm skin. Local heating was caused with a thermostatic probe holder set at 40 degrees C. We studied the perfusion value and its two components, velocity and concentration. All registrations were also subjected to frequency analysis. Laser Doppler values were generally higher in the fingertip than in forearm skin. Heating caused increased values at both locations. Concentration increased relatively more than velocity and this was most obvious in the forearm. There were only slight differences in response between superficial and deeper vascular components. Frequency analysis revealed a peak in perfusion and velocity obviously related to the heartbeat. Movement of the column of blood thus reached the peripheral vascular network without changing concentration. We conclude that local heating increases skin blood flow in fingertip and forearm skin by different adjustments of blood cell concentration and velocity, presumably depending on differing vascular anatomy and physiological control, but differences are of a rather minor character. Furthermore, responses differ just slightly in superficial compartments as probed with fibers separated up to 0.25 mm.

Islet autoantibodies in cord blood from patients who developed type 1 diabetes mellitus at 15-30 years of age.

Islet cell autoantibodies are early markers for type 1 diabetes. The aim of this study was to determine whether islet autoantibodies were present at birth in young adults who developed type 1 diabetes at 15-30 years of age. Cord blood sera from 30 patients who developed type 1 diabetes between 15 and 25 years of age and sera from 320 randomly selected control children were tested for islet cell antibodies (ICA) by indirect immunofluorescence and autoantibodies against the 65 kD isoform of glutamic acid decarboxylase (GADA), islet cell antigen-2 (IA-2A) and insulin (IAA) by radiobinding assays. The young adults who developed type 1 diabetes did not differ from controls in the cord blood prevalence of any of the four islet autoantibodies. This is in contrast to our previous findings that children who developed type 1 diabetes below 15 years of age had an increased prevalence of cord blood islet autoantibodies. Our present data suggest that, in contrast to children, pre- and perinatal risk factors are less likely to be involved in the development of type 1 diabetes in young adults.

Signs of nephropathy may occur early in young adults with diabetes despite modern diabetes management: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS).

OBJECTIVE: To estimate the occurrence of early-onset renal involvement in a nationwide population-based cohort of young adults with diabetes in Sweden and relate the findings to glycemic control, type of diabetes, sex, smoking, and blood pressure. RESEARCH DESIGN AND METHODS: The Diabetes Incidence Study in Sweden aims to register all incident cases of diabetes in the age-group 15-34 years. In 1987-1988, 806 patients were reported and invited to participate in a follow-up study focusing on microvascular complications. Of them, 469 subjects participated. The assessment was based on questionnaires (n = 469), blood samples (n = 424), urine samples (n = 251) and, when appropriate, medical records (n = 186). RESULTS: During the follow-up time, median 9 years (range 6-12), 31 of 469 patients (6.6%) with incipient or overt diabetic nephropathy (i.e., micro- or macroalbuminuria) were found, 24 of 426 (5.6%) in type 1 and 7 of 43 (16%) in type 2 diabetic subjects (P = 0.016). Additionally, 24 of 31 patients (77%) had microalbuminuria and 7 (23%) had macroalbuminuria, which mainly occurred in patients with type 2 diabetes. In a Cox regression analysis, high mean HbA(1c) during the follow-up period and high blood pressure at follow-up increased the risk of developing signs of nephropathy (P = 0.020 and P = 0.003, respectively). Compared with patients with type 1 diabetes, those with type 2 diabetes tended to have an increased risk of renal involvement (P = 0.054) when adjusting for sex, tobacco use, glycemic control, and blood pressure. CONCLUSIONS: Despite modern treatment and self-monitoring of blood glucose, young adult patients with diabetes may still develop renal involvement during the first 10 years of diabetes duration. Inadequate HbA(1c), high blood pressure, and type 2 diabetes appear to be risk markers for early occurrence of diabetic nephropathy.

Endoneurial capillary abnormalities presage deterioration of glucose tolerance and accompany peripheral neuropathy in man.

To explore whether microangiopathy is associated with disturbed glucose tolerance and peripheral neuropathy, we assessed endoneurial capillary morphology in sural nerve biopsies from men with diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). Baseline morphology was related to glucose tolerance and neuropathy at baseline and at follow-up 6 years later. Capillary density (in number per millimeters squared) at baseline was higher in subjects with diabetes (n = 10) compared with those with NGT (n = 5) at follow-up (median [interquartile range]) (86.0 [24.3] vs. 54.9 [17.1]; P = 0.0200) and in those progressing from IGT to diabetes (n = 4) compared with those with persistent IGT (n = 4) (86.7 [25.2] vs. 54.1 [14.6]; P = 0.0433). The capillary luminal area (in micrometers squared) was lower in subjects with NGT progressing to IGT (n = 2) or subjects with IGT progressing to diabetes (n = 3) compared with subjects with constant NGT (n = 6) or constant IGT (n = 4) (11.9 [2.4] vs. 20.8 [7.8]; P = 0.0201). The capillary basement membrane area (in micrometers squared) was increased in patients with peripheral neuropathy (n = 10) compared with those without (n = 7) (114.6 [68.8] vs. 75.3 [28.7]; P = 0.0084). In conclusion, increased capillary density was associated with current or future diabetes, decreased capillary luminal area with future deterioration in glucose tolerance, and increased basement membrane area with peripheral neuropathy.

Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients.

OBJECTIVE: To evaluate whether treatment with insulin in recently diagnosed type 2 diabetes is advantageous compared with glibenclamide treatment. RESEARCH DESIGN AND METHODS: Beta-cell function, glycemic control, and quality of life were monitored over 2 years in 39 patients with islet cell antibody-negative type 2 diabetes diagnosed 0-2 years before inclusion in a Swedish multicenter randomized clinical trial. Patients were randomized to either two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide (3.5-10.5 mg daily). C-peptide-glucagon tests were performed yearly in duplicate after 2-3 days of temporary withdrawal of treatment. RESULTS: After 1 year the glucagon-stimulated C-peptide response was increased in the insulin-treated group by 0.14 +/- 0.08 nmol/l, whereas it was decreased by 0.12 +/- 0.08 nmol/l in the glibenclamide group, P < 0.02 for difference between groups. After 2 years, fasting insulin levels were higher after treatment withdrawal in the insulin-treated versus the glibenclamide-treated group (P = 0.02). HbA(1c) levels decreased significantly during the first year in both groups; however, at the end of the second year, HbA(1c) had deteriorated in the glibenclamide group (P < 0.01), but not in the insulin-treated group. The difference in evolution of HbA(1c) during the second year was significant between groups, P < 0.02. A questionnaire indicated no difference in well-being related to treatment. CONCLUSIONS: Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.