bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and subcellular localization of the Na+/H+ exchanger and a novel related protein in the endocrine pancreas and adrenal medulla
Authors: Moulin Pierre , Guiot Yves , Jonas Jean-Christophe , Rahier Jacques , Devuyst Olivier , Henquin Jean-Claude
Published: March 2007

Na+/H+ exchangers (NHE) constitute a family of membrane antiporters that contribute to the regulation of cellular pH and volume in many tissues, including pancreatic islets. We investigated the molecular identity of NHE in rodent and human endocrine pancreas, and determined its cellular and subcellular localization. NHE1 was the most abundantly expressed isoform in rat islets, and was also expressed in mouse and human islets. By western blot, an antiserum raised against the C-terminus end of NHE1 confirmed the presence of a ~100 kDa protein corresponding to NHE1 in islets and unexpectedly unveiled the existence of a ~65 kDa cross-reactive NHE1-related protein. By immunohistochemistry, the antiserum labelled the membranes of pancreatic acini and ducts, but also diffusely stained the cytoplasm of insulin, glucagon and somatostatin cells as well as endocrine cells of the adrenal medulla. Electron microscopy localized the NHE1 immunoreactivity in the membrane of secretory granules, an unexpected finding supported by a decrease in immunohistochemical signal in degranulated β-cells. Islets of Slc9A1swe/swe mice, which lack full NHE1 protein, were found to express an mRNA corresponding to the 3′ end of NHE1 as well as the ~65 kDa protein. They still showed the cytoplasmic labelling but no plasma membrane was stained. We conclude that both the full-length and the shorter-splice variant of NHE1 are expressed in all cell types of the endocrine pancreas and in the adrenal medulla of rodents and humans. The complete protein is addressed to the plasma membrane and the shorter one to the membrane of secretory granules where its function remains to be established.
Self-Efficacy in Adolescent Girls and Boys With Insulin-Dependent Diabetes Mellitus
Authors: Grossman Hildreth Youkilis , Brink Stuart , Hauser Stuart T
Published: March 2007

Adolescents with insulin-dependent diabetes mellitus (IDDM) face increasing responsibilities for managing their own treatment. For some, implementing their treatment regimen enhances diabetes selfefficacy beliefs because they welcome the chance to exert control over their illness. Other adolescent patients, however, feel overwhelmed and helpless. We developed the self-efficacy for diabetes scale (SED) with a sample of adolescent boys (n = 34) and girls (n = 34) with IDDM. High reliability (internal consistency) and evidence for criterion validity were obtained for this measure, because SED scores predicted metabolic control. In addition, construct validity was established, because SED scores were related to theoretically relevant measures of locus of control and self-esteem. Although they showed similar expectancies for diabetes self-efficacy, girls had significantly positive correlations between their SED scores and metabolic control, whereas boys did not. We offer a new instrument for studying adolescent patient perceptions and physical health.
Urinary N-Acetyl-β-D-Glucosaminidase Activity Does Not Predict Development of Diabetic Nephropathy
Authors: Agardh Carl-David , Tallroth Gustav , Hultberg Björn
Published: March 2007

Urinary activity of N-acetyl-β-D-glucosaminidase (NAG) has been suggested as a marker for diabetic nephropathy. In this study, urinary activity of NAG was measured with an interval of 5 yr in 36 insulin-dependent diabetic subjects to evaluate its predictive value for development of diabetic nephropathy. During the observation period, 9 patients developed detectable signs of diabetic nephropathy. In these patients, urinary albumin concentration had increased to 503 ± 185 mg/L, compared to 16 ± 1 mg/L in patients without nephropathy (P < .01; means ± SE), and the fractional albumin excretion rate was 0.21 ± 0.07 × 10∼3, compared to 0.01 ± 0.00 × 10∼3 (P < .01). However, the activity of urinary NAG was not different in these patients compared with the patients without nephropathy (0.69 ± 0.15 and 0.61 ± 0.09 U/mmol creatinine, respectively). Furthermore, no increase in the activity of urinary NAG was seen during the observation period in either group. We concluded that the urinary activity of NAG is not related to the development of microalbuminuria and therefore cannot be used as a predictor for the development of diabetic nephropathy.
Effects of Accidental Intramuscular Injection on Insulin Absorption in IDDM
Authors: Frid Anders , Gunnarsson R , Güntner P , Linde B
Published: March 2007

Recent studies have shown that with the injection technique presently recommended to diabetic patients, accidental intramuscular injection of insulin is liable to occur quite frequently. In this study, the simultaneous absorption of 125I-labeled soluble human insulin (5 U) from subcutaneous and intramuscular injection sites in the thigh and abdomen was measured for 3 h in 10 insulin-dependent diabetic subjects to evaluate the importance of accidental intramuscular injection for insulin absorption in the resting state. Injection sites were located with computed tomography of the thigh and abdomen. From a superficial part of the thigh musculature, the absorption rate was at least 50% higher than from the adjacent subcutaneous tissue, the time until 50% of the initial activity remained (t1/2) being 123 ± 14 and >180 min, respectively (P < .001). No difference in absorption rates was found between the two tissues in the abdomen (t1/2 84 ± 6 vs. 93 ± 7 min, NS). The results suggest that in the thigh, accidental intramuscular injections will considerably increase the variability of insulin absorption and may impair glycemic control in insulin-dependent diabetic patients. Furthermore, the influence of accidental intramuscular injection on insulin absorption seems to vary among injection regions.
Beat-to-Beat Blood Pressure Response in Asymptomatic IDDM Subjects
Authors: Goldstein Iris B , Naliboff Bruce D , Shapiro David , Frank Harrison JL
Published: March 2007

Nine insulin-dependent diabetic (IDDM) patients (aged 25–37 yr) with no symptoms of autonomic neuropathy and 15 healthy control subjects (aged 26–39 yr) were studied at rest and during tests of Valsalva maneuver, deep breathing, cold pressor, and postural change from sitting to standing. Continuous (beat-to-beat) measures were taken of heart rate, systolic blood pressure, diastolic blood pressure, and skin conductance. The diabetic patients were differentiated from the control group by the following: less variability in diastolic blood pressure during deep breathing, failure to exhibit diastolic blood pressure decreases during recovery from a cold pressor stimulus, a flatter blood pressure response pattern when changing from sitting to standing, and a smaller standing ratio (maximum/minimum) for R-R interval. Among the patients, age was negatively correlated with systolic and diastolic standing ratios and diastolic blood pressure variability during deep breathing. By use of the tracking cuff, a method of continuously recording blood pressure noninvasively, we have been able to assess subtle blood pressure changes, thereby revealing signs of sympathetic dysfunction in a group of relatively young diabetic patients with no symptoms of neuropathy. The tracking-cuff method of recording blood pressure has potential in further research on autonomic functioning in diabetic patients.
Comparison of Plasma Glucose and Insulin Responses to Mixed Meals of High-, Intermediate-, and Low-Glycemic Potential
Authors: Hollenbeck Clarie B , Coulston Ann M , Reaven Gerald M
Published: March 2007

Although plasma glucose and insulin responses have been shown to vary considerably when either normal subjects or patients with non-insulin-dependent diabetes mellitus (NIDDM) consume different carbohydrate-rich foods, it has been difficult to demonstrate this phenomenon when the same foods have been incorporated into a single mixed meal. To pursue this issue further, plasma glucose and insulin concentrations were determined at hourly intervals from 0800 to 2100 h in NIDDM patients in response to three meals (breakfast, lunch, and dinner) calculated to be of low-, intermediate-, and high-glycemic potency. The total integrated glucose response (mean ± SE) during the day the low-glycemic meals were ingested was ∼7% lower (2500 ± 246 mg · dl−1 · h−1) than on the days patients ate either the intermediate- (2701 ± 280 mg · dl−1 · h−1) or high- (2718 ± 311 mg · dl−1 · h−1) glycemic meals. When these data were analyzed by meal, it became apparent that the plasma glucose response to breakfast and dinner were essentially identical after consumption of the meals of either low-, intermediate-, or high-glycemic potency. Thus, the modest attenuation of the day-long glycemic response on the day patients ate the lowglycemic meal was due to a reduction in plasma glucose concentration after lunch. The day-long plasma insulin responses to the meals of different glycemic potency were qualitatively similar.
Effects of BAYm 1099, New α-Glucosidase Inhibitor, on Acute Metabolic Responses and Metabolic Control in NIDDM Over 1 Mo
Authors: Samad Abu HB , Ty Willing Thomas S , Alberti K George MM , Taylor Roy
Published: March 2007

To examine the clinical role of BAYm 1099, 15 diettreatednon-insulin-dependent diabetic (NIDDM) subjects were randomized to start drug (50 mg 3 times/ day) or placebo after a 4-wk run-in period in a doubleblind crossover study. Treatment periods (4 wk) were separated by a 2-wk washout period. During the last week of each treatment period, three test meals (TMs) were administered: 60 g starch (TM1), 25 g sucrose (TM2), and combined 60 g starch and 25 g sucrose (TM3). Twelve subjects completed the study. The peak postprandial blood glucose, lactate, and pyruvate levels (means ± SE) were significantly lower with active drug after all test meals, particularly TM2 (11.3 ±1.0 vs. 14.3 ± 1.4 mM, P <.001; 1.53 ± 0.20 vs. 2.48 ± 0.17 mM, P < .001; and 105.1 ± 17.6 vs. 147.6 ± 11.1 μM, P < .05, respectively. Peak blood glucose levels were significantly delayed. However, fasting blood glucose, HbA1, fructosamine, and cholesterol did not change during active treatment (10.0 ±1.0 vs. 9.9 ±1.0 mM, 10.0 ± 0.7 vs. 9.4 ± 0.7%, 2.44 ± 0.10 vs. 2.37 ± 0.07 mmol/100 g protein, and 6.7 ± 0.3 vs. 6.5 ± 0.3 mM, P NS). Flatulence and diarrhea were severe in 2 subjects, requiring termination of study. Thus, in NIDDM, BAYm 1099 was effective in diminishing and delaying postprandial excursions of blood glucose, lactate, and pyruvate after high- and low-sucrose meals, but overall metabolic control remained unchanged. The results of acute studies on food absorption cannot be extrapolated to predict longer-term effects on glycemic control in diet-treated NIDDM subjects.
Weight Gain Associated With Intensive Therapy in the Diabetes Control and Complications Trial
Authors:   The DCCT Research Group
Published: March 2007

Identifiable risks such as increased frequency of hypoglycemia accompany the treatment of insulindependent diabetes mellitus (IDDM) with intensive insulin therapy. During yr 1 of the Diabetes Control and Complications Trial (DCCT), weight gain was identified as a sequela of intensive insulin therapy. The DCCT is a multicenter controlled clinical trial designed to determine the long-term effects of two different diabetes treatment regimens on the early vascular and neurologic complications of IDDM. Subjects randomized to the intensive treatment regimen gained significantly more weight (5.1 ± 4.6 kg) than the standard treatment subjects (2.4 ± 3.7 kg, P < .0001) during the 1st yr of therapy. Higher baseline HbA1c levels and greater decrements in HbA1c during intensive therapy were both associated with greater weight gain. In addition, intensively treated subjects with one or more severe hypoglycemic episodes gained more weight than the intensively treated subjects with no severe episodes. There was no relationship between reported caloric intake or exercise level and the weight changes. These data suggest that improved utilization of calories through a decrease in glycosuria and perhaps other mechanisms led to the weight gain in the intensively treated subjects. The results from the 1st yr of experience in the DCCT indicate that weight gain accompanies efforts to lower blood glucose levels with intensive insulin therapy. Because of the potential adverse consequences of undesirable weight gain, including diminished long-term compliance with therapy and an adverse effect on blood pressure and lipid status, efforts to prevent undesirable weight gain in the intensively treated group of the DCCT are being pursued.
Exocrine Pancreatic Function in Tropical Fibrocalculous Pancreatic Diabetes
Authors: Mohan Viswanathan , Snehalatha Chamukuttan , Ahmed Mohamed Riazuddin , Madanagopalan Nagendram , Chari Suresh , Jayanthi Venkatraman , Malathi Sathyasekaran , Ramachandran Ambady , Viswanathan Moopil
Published: March 2007

Exocrine pancreatic function was studied by fecal chymotrypsin test in three groups of diabetic patients seen in southern India. Exocrine pancreatic insufficiency, as shown by low fecal chymotrypsin levels, was seen in 87.5% of patients with fibrocaiculous pancreatic diabetes (FCPD), in 23.5% of insulindependent diabetes mellitus patients, and in 4.5% of non-insulin-dependent diabetes mellitus patients. There was no correlation between fecal chymotrypsin levels and serum amylase, serum lipase, age, body mass index, duration of diabetes, fasting plasma glucose, or glycosylated hemoglobin levels. The fecal chymotrypsin test is a useful additional investigation for the diagnosis of FCPD found in tropical countries.
Augmentation of Atrial Contribution to Left Ventricular Filling in IDDM Subjects as Assessed by Doppler Echocardiography
Authors: Airaksinen K E Juhani , Koistinen M Juhani , Ikäheimo Markku J , Huikuri Heikki V , Korhonen Ulla , Pirttiaho Heikki , Linnaluoto Markku K , Takkunen Juha T
Published: March 2007

Left ventricular diastolic function was assessed by pulsed Doppler echocardiography in 21 subjects (mean age 48 yr) with insulin-dependent diabetes mellitus (IDDM) and without evidence of ischemic heart disease and in 21 healthy control subjects of similar age and sex distribution. The peak mitral valve flow velocities during the early rapid filling phase (E) and during late atrial filling (A) were measured, and the ratio of these peak flow velocities (E:A) was calculated. E was similar in both groups, but A was higher (P < .01) in the diabetic group. Thus, E A was lower (1.19 ± 0.24 vs. 1.65 ± 0.67; P <.01) in the diabetic subjects than in the control subjects. On subgroup analysis, 6 patients with cardiac autonomic neuropathy had lower E:A than the patients with no such disorder (0.99 ± 0.15 vs. 1.29 ± 0.25; P < .05). E A was not related to the duration of diabetes, presence of retinopathy, HbA,, or blood glucose levels. In conclusion, the atrial contribution to left ventricular filling seems to be augmented in diabetic subjects. This finding indirectly supports the view that left ventricular compliance is already reduced in asymptomatic diabetic subjects.
Visual Evoked Potentials in Diabetic Patients
Authors: Algan Michel , Ziegler Olivier , Gehin Philippe , Got Isabelle , Raspiller Antoine , Weber Michel , Genton Pierre , Saudax Etienne , Drouin Pierre
Published: March 2007

Visual evoked potentials (VEPs) were assessed in 50 adult type I (insulin-dependent) and 19 type II (noninsulin-dependent) diabetes mellitus patients and in 54 controls. P100 wave latency was significantly longer in diabetic patients (P < .001). Twenty-eight percent of diabetic patients had P100 wave latencies above the normal range. There was no correlation between P100 latency and type or duration of diabetes mellitus, quality of metabolic control, or presence of degenerative complications. The significance of VEP abnormalities in diabetes mellitus remains speculative.
Dawn Phenomenon and Somogyi Effect in IDDM
Authors: Stephenson Judith M , Schernthaner Guntram
Published: March 2007

We examined the clinical relevance of a rise in fasting blood glucose (BG) between 0300 and 0600 in 97 patients with insulin-dependent diabetes mellitus (IDDM) receiving sequentially conventional (CT) and basal-bolus (BBIT) insulin therapies and assessed the impact of one potential causal factor, i.e., posthypoglycemic hyperglycemia, with 231 BG profiles (97 during CT, 134 during BBIT) in which BG was measured every 3 h over a 24-h period. A rise in BG between 0300 and 0600 occurred in 157 of 231 (68%) profiles. The mean magnitude of this rise was 56 ±39 mg/dl and was lower (P < .05) during BBIT (48 ± 35 mg/dl, n = 97) than CT (62±43 mg/dl, n = 97). A dawn rise (between 0300 and 0600) >50 mg/dl occurred in 40 of 97 (41%) profiles during CT and 26 of 97 (27%) during BBIT (P < .05). When all profiles were grouped according to the magnitude of this rise in BG, the mean daytime BG (from 0900 to 1800) was higher (P < .05) after an 0300–0600 BG rise >50 mg/dl compared with groups of profiles showing either a fall in BG or a rise <50 mg/dl; a rise in BG between 0300 and 0600 correlated (r = .38, P < .0001) with the subsequent mean daytime BG. Nocturnal hypoglycemia (BG <60 mg/dl) recorded at 2400 and/or 0300 occurred in 57 of 231 (25%) profiles. After nocturnal hypoglycemia, the highest BG recorded before breakfast was only 215 mg/dl, and the mean BG at 0600 was considerably lower (P < .0001) in profiles showing at least one episode of nocturnal hypoglycemia (116 ± 45 mg/dl, n = 57) compared with all profiles in which no nocturnal hypoglycemia was detected (174 ± 85 mg/dl, n = 174). In addition, postbreakfast BG levels at 0900 were lower (P < .0001) after nocturnal hypoglycemia (171 ± 87 mg/dl, n = 57) than when no nocturnal hypoglycemia was detected (211 ± 91 mg/dl, n = 174). We conclude that a dawn rise in BG commonly occurs in IDDM patients receiving either CT or BBIT. A dawn BG rise >50 mg/dl may lead to significant exacerbation of daytime hyperglycemia. Nocturnal hypoglycemia does not contribute to morning hyperglycemia, but conversion from CT to BBIT can achieve a modest reduction in the frequency and magnitude of an early-morning rise in BG.
Rising Incidence of IDDM in Europe
Authors: Bingley Penelope J , Gale Edwin A M
Published: March 2007

A rising incidence of insulin-dependent diabetes mellitus (IDDM) has been reported in many northern European countries, with a rate equivalent to a doubling time of 20–30 yr in some. North American and Japanese studies report a similar trend, although they are less uniform in their findings. Although the number of genetically susceptible individuals within these populations has increased, the rapidity of the change suggests that environmental factors are responsible. If these could be identified, primary prevention might become possible.
Relative Sweetness of Fructose Compared With Sucrose in Healthy and Diabetic Subjects
Authors: Fontvieille Anne Marie , Faurion Annick , Helal Isaad , Rizkalla Salwa W , Falgon Sophie , Letanoux Martine , Tchobroutsky Georges , Slama Gerard
Published: March 2007

Fructose is credited with some advantages over sucrose: it causes less of an increment in plasma glucose and insulin response, and the taste is sweeter. We reevaluated the latter property with a new methodology (the “up and down” method adapted from Dixon) in 33 healthy subjects, 17 insulin-dependent diabetes mellitus (IDDM) patients, and 12 non-insulin-dependent diabetes mellitus (NIDDM) patients. Sweetening potency was determined over 2–3 test sessions in each subject. Results are expressed in percent as the relative sweetness (R) of fructose (F) over sucrose (S), taken as reference. In the first set of experiments, with a 30-g/L sucrose-water solution at pH 7, we found that R values were similar for healthy subjects (102 ± 8%) and diabetic subjects (106 ± 7%) (P < .05). No significant difference between IDDM and NIDDM patients was observed. In a second set of experiments, performed in healthy subjects only, R was increased in acid water (114%; P < .01), in lemon juice (136%; P < .001), in water at 2°C (130%; P < .001), and in coffee at 2°C (120%; P < .02); mean values were decreased in grapefruit juice (77%; P < .001), in water at 43°C (88%; P < .01), and in coffee at 53°C (87%; P < .001). We found that the test methodology had a very satisfactory intrasubject reproducibility (coefficient of variation [C.V.] < 8%) but a very wide intersubject variability (C.V. ≃ 32%). We conclude that fructose has either an equal, higher, or lower relative sweetness compared with sucrose, depending on the physical and chemical characteristics of the solutions. The results were unpredictable for one given subject, but fructose seemed regularly sweeter in cold beverages than in hot ones. Diabetic individuals found fructose slightly but significantly sweeter than sucrose, but it is doubtful that this modest difference has any clinical implications.
Diagnosing Gestational Diabetes Mellitus: Is the Gold Standard Valid?
Authors: Naylor C David
Published: March 2007

In North America, gestational diabetes mellitus (GDM) is diagnosed from a 100-g oral glucose tolerance test (OGTT) with criteria proposed by the National Diabetes Data Group (NDDG). These criteria were derived in the 1950s from an unrepresentative sample of women tested predominantly in the latter stages of pregnancy. The original studies did not check for reproducibility of OGTT results. Measurements were made with the Somogyi-Nelson whole-blood glucose technique, and test translation errors are present in the threshold values proposed for modern plasma glucose oxidase methods. Whereas GDM is now diagnosed with a view to adverse m ternal-fetal outcomes, the criteria were chosen to reflect maternal risk of developing glucose intolerance as shown by a 75-g OGTT in the nonpregnant state over the ensuing 8 yr. For that outcome, the positive predictive value of the criteria was only 36.1%, and this is a marked overestimate, because the study cohort was a highly selected group with an increased incidence of glucose intolerance both during and after pregnancy. The criteria are also conceptually flawed in that they impose a dichotomous definition of normal and abnormal on gestational glucose tolerance, when the risk of adverse maternal-fetal outcomes and later diabetes mellitus should logically be graded upward with higher values on the gestational OGTT and with the degree of fasting hyperglycemia. Although NDDG criteria merit continued use for lack of a better alternative, new diagnostic criteria for GDM should be derived and validated.
Intranasal Glucagon as Remedy for Hypoglycemia: Studies in Healthy Subjects and Type I Diabetic Patients
Authors: Pontiroli Antonio E , Calderara Anna , Pajetta Elena , Alberetto Miriam , Pozza Guido
Published: March 2007

Intranasal glucagon can raise blood glucose levels in healthy subjects. The aims of this study were to 7) compare the hyperglycemic effect of intranasal and intramuscular glucagon in healthy subjects and type I (insulin-dependent) diabetes patients during euglycemic conditions and 2) test the efficacy of intranasal and intramuscular glucagon in counteracting hypoglycemic episodes in insulin-treated diabetic patients. Intranasal glucagon raised blood glucose levels in both healthy subjects and type I diabetic patients, the effect of intramuscular glucagon being similar for the first 30 min and higher thereafter. Intranasal glucagon was also quicker acting than oral glucose in healthy subjects. Intranasal glucagon raised blood glucose levels in patients with hypoglycemic episodes, although less effectively than intramuscular glucagon. These data indicate intranasal glucagon as a possible emergency remedy for self-medication in insulin-treated patients prone to hypoglycemic episodes.
Relationship Between Hyperglycemia and Cognitive Function in Older NIDDM Patients
Authors: Reaven Gerald M , Thompson Larry W , Nahum David , Haskins Edmund
Published: March 2007

The nature and extent of cognitive impairment was examined in 29 healthy elderly subjects (mean age 69.8 yr) with non-insulin-dependent diabetes mellitus (NIDDM) and 30 demographically similar nondiabetic community volunteers (mean age 68 yr). Measures of verbal learning, abstract reasoning, and complex psychomotor functioning were performed more poorly by diabetic than nondiabetic subjects. Conversely, there were no between-group differences in performance on tasks involving pure motor speed and simple verbal abilities. Within the diabetic group, individuals with poorer metabolic control performed more poorly on tasks involving learning, reasoning, and complex psychomotor performance, although this relationship was not evident for simple verbal or motor tasks. These data indicate that older people with NIDDM who are functioning well and perceive themselves as in good health are likely to manifest greater deficits than healthy elderly people in processing complex verbal or nonverbal material. Possible explanatory mechanisms are discussed, and directions for future research are explored.
Incidence of IDDM During 1984–1986 in Population Aged <30 Yr: Residents of Turin, Italy
Authors: Bruno Graziella , Merletti Franco , Pisu Elisabetta , Pastore Guido , Marengo Claudio , Pagano Gianfranco
Published: March 2007

The goal of this study was to measure the incidence of insulin-dependentdiabetes mellitus (IDDM) during 1984–1986 in residents of Turin, Italy, aged <30 yr. The primary data source was the list of all subjects diagnosed with IDDM who attended diabetes clinics in Turin. Other data sources were the general register of death certificates, the list of hospital discharges, andthe computerized data base of insulin prescriptions. Eighty incident cases of IDDM were identified during the study in 1,130,284 person-yr for those <30 yr of age. Ageadjusted (world standard) incidence rates were 8.05, 8.10, and 6.96/100,000 in the age-groups 0–14, 0–19, and 0–29 yr, respectively. Estimated completeness of the primary data source compared with all other data sources was 91%, whereas the estimated completeness of ascertainment ofthe registry was 99%. Incidence rates of IDDM in northern Italy compare withthose of European countries with low-medium incidence. A population-based register is being established for the province of Turin (951,445 inhabitants aged 0–29 yr) for the collection of incident cases since 1984.
Complement-Fixing Antibodies to Sympathetic and Parasympathetic Tissuesin IDDM: Autonomic Brake Index and Heart-Rate Variation
Authors: Rabinowe Steven L , Brown Florence M , Watts Michael , Smith Ana Maria
Published: March 2007

We describe herein complement-fixing anti-adrenal medullary (CF-ADM) andanti-sympathetic ganglia (CFSG) antibodies in insulin-dependent diabetes mellitus (IDDM). This study describes complement-fixing antivagus (CF-V) nerve antibodies and their relationship to the cardiovascular autonomic brake index (a measure of transient decrease in heart rate during the 1st min after a tilt), and R-R interval variation with deep breathing. CF-V was detectable in 7 of 83 (8.4%) subjects with IDDM aged 1.5–65.5 yr (mean ± SE 28.7± 1.8 yr) and duration of diabetes 0–47 yr (11.8 ± 1.4 yr). Seventy-six nondiabetic subjects (aged 10–65 yr) all had negative CF-V scores. CF-V scores correlated with CF-ADM (0–16 yr of IDDM, r = 0.61, P < 0.0001) and CF-SG (r = 0.39, P < 0.05). Seventy IDDM subjects (aged 28 ± 5 yr, duration of diabetes 17 ± 3 yr) without proteinuria or proliferative retinopathy were screened for CF-ADM, CF-SG, and CF-V antibodies. Five of 70 (7.1%) had CF-SG only (negative for CF-ADM and CF-V). Brake indices ranged from 14.7 to 51.3 (37.3 ± 6.9). Three of 70 (4.2%) had CF-ADM only, with brake indices from 26.9 to 45.1 (32.9 ± 6.1). Four of 70 (5.7%) had CF-V antibodies only, with brake indices of 12.7–17.3 (15.1 ± 1.1). Subjects with CF-SG or CF-ADM (antisympathetic) had higher brake indices than subjects with CF-V (anti-parasympathetic) antibodies (P < 0.03). Subjects with CF-SG had higher brake indices than those with CF-V (P < 0.04). The heart-rate variation with deep breathing was 23.3 ± 10.0 in subjects with CF-V and 45.66 ± 5.1 in the CF-SG+ and/or CF-ADM+ group (P < 0.03). This study demonstrates CF-V antibodies in IDDM and their association with a lower brake index and R-R interval variation compared with patients with sympathetic nervous system autoimmunity.
Differences Between Prebreakfast and Late Afternoon Glycemic Responses to Exercise in IDDM Patients
Authors: Jeffrey Ruegemer J , Squires Ray W , Marsh Harold M , Haymond Morey W , Cryer Philip E , Rizza Robert A , Miles John M
Published: March 2007

Little information is available regarding the optimal timing of exercise in insulin-dependent diabetes mellitus (IDDM) patients. In this study, six IDDM patients receiving ultralente-based intensive insulin therapy were studied during 30 min of exercise (∼60% Vo2max), before breakfast, and at 1600. On two other occasions, they were studied at rest. Plasma glucose increased from 6.7 ± 0.4 to 9.1 ± 0.4 mM during morning exercise (P < 0.01). In contrast, mean plasma glucose did not change during afternoon exercise (≸ = 0.3 ± 0.5 mM, NS); however, there was a 0.3- to 1.0-mM decrease in three subjects. The observed difference in the glycemic response to exercise could not be explained on the basis of changes in plasma glucagon, growth hormone, norepinephrine, or epinephrine. Plasma cortisol was higher (P < 0.02) in the morning than in the afternoon, and plasma free-insulin concentrations were lower (P < 0.05). These data indicate that the risk of exerciseinduced hypoglycemia is lowest before breakfast. The reason for the divergent glycemic responses to exercise is not entirely clear but may be related to the observed differences in free-insulin concentrations. Because of the lower risk of hypoglycemia, our results suggest prebreakfast exercise may be preferable for some IDDM patients receiving intensive insulin therapy. Whether these findings are relevant to patients receiving other types of insulin therapy will require further investigation.
Glucose Transport and Glucose Transporters in Muscle and Their Metabolic Regulation
Authors: Klip Amira , Pâquet Michel R
Published: March 2007

Skeletal muscle is the primary tissue responsible for insulin-dependent glucose uptake in vivo; therefore, glucose uptake by this tissue plays an important role in determining glycemia. Glucose uptake in muscle occurs by a system of facilitated diffusion involving at least two distinct glucose transporters, GLUT-1 and GLUT-4. Both bind the fungal metabolite and inhibitor of glucos transport cytochalasin B. In human skeletal muscle, both types of transporters are detected immunologically, and corresponding mRNA transcripts of both transporter forms are detected. In human skeletal muscle cells in culture, in which contamination by other tissues is ruled out, a 50,000-M, polypeptide is photolabeled with cytochalasin B. In rat skeletal muscle, acute treatment with insulin in vivo increases glucose-transport activity and the number of specific cytochalasin B-binding sites at the plasma membrane. In mildly diabetic (streptozocin-induced) rats, the number of cytochalasin B-binding sites is decreased in total membranes, and preferentially in the plasma membrane. In response to acute insulin treatment, however, there is still recruitment of glucose transporters to the plasma membrane from an intracellular membrane store. Hence, migration of transporters does occur in this form of diabetes. In L6 muscle cells in culture, acute treatment (1 h) with insulin causes recruitment of glucose transporters to the plasma membrane, and prolonged exposure to insulin or to glucose-deprived medium causes increased expression of GLUT-1 mRNA and GLUT-1 protein. Prolonged exposure (24 h) to high glucose in the medium causes a decrease in the number of glucose transporters in the plasma membrane. Hence, in those cells the expression of the GLUT-1 glucose transporter is modulated by insulin.
Hypoglycemia Risk During Exercise After Intramuscular Injection of Insulin in Thigh in IDDM
Authors: Frid Anders , Östman Jan , Linde Birgitta
Published: March 2007

The influence of bicycle exercise (60% of W170 [working capacity at a pulse rate of 170 beats/min]; 40 min) on the absorption of 125I-labeled fast-acting insulin (10 U; Actrapid human insulin) after intramuscular compared with subcutaneous injection in the thigh was studied on 2 consecutive days in 10 insulin-dependent diabetes mellitus (IDDM) patients. Insulin absorption was measured as disappearance of radioactivity (1st-order elimination rate constants) by continuous external monitoring and as appearance of plasma free immunoreactive insulin (IRI). Subcutaneous adipose tissue blood flow (ATBF) and skeletal muscle blood flow (MF) were measured concomitantly in the contralateral thigh with the raXe wash-out technique. Plasma glucose was determined intermittently. The rate constant for 125l-insulin increased during exercise from 0.46 ± 0.08 to 1.17 ± 0.14%/min after intramuscular injection (P < 0.001) and from 0.31 ± 0.05 to 0.45 ± 0.09%/min (NS) after subcutaneous injection. The rate constant of 125I-insulin from muscle remained elevated during the 80-min recovery period. The peak plasma free-IRI value was 39 mU/L higher, the area under the IRI curve was ∼80% greater, and the decrease in plasma glucose was ∼2 mM greater after intramuscular injection. Whereas MF increased fivefold, ATBF did not rise significantly during exercise. The results demonstrate that intramuscular compared with subcutaneous thigh injection of insulin followed by bicycle exercise induces a marked increase in insulin absorption and a substantial fall in plasma glucose. Because accidental intramuscular injection of insulin may occur frequently, these findings highlight a previously unobserved risk for an unexpected decrease in plasma glucose levels in connection with leg exercise in IDDM patients. This risk could be minimized by injection into a skin fold or by use of shorter needles for thigh injection.
Usefulness of Biochemical Screening of Diabetic Patients for Hemochromatosis
Authors: O'Brien Timothy , Barrett Brendan , Murray Donal M , Dinneen Sean , O'Sullivan Denis J
Published: March 2007

We assessed the prevalence of previously unrecognized hemochromatosis among patients in whom diabetes mellitus was diagnosed after the age of 30 yr, and we evaluated the positive predictive value of biochemical screening tests for hemochromatosis in diabetic subjects. Thirty-eight of 572 patients screened (6.6%) had a serum ferritin level >324 μg/L; 16 patients had normal levels on repeat testing. Four patients′ serum ferritin levels fell to <400 μg/L. Seven of 18 patients with a persistently elevated serum ferritin level did not undergo a liver biopsy because of a recognized cause of hyperferritenemia (carcinoma, alcoholism, or systemic lupus erythematosus). The diagnosis of hemochromatosis seemed certain in 1 of 3 patients who were not biopsied for technical reasons. Of 8 patients biopsied, 2 had hemochromatosis, 4 had fatty liver, 1 had hemosiderosis, and 1 had a chronic inflammatory cell infiltrate with no iron deposition. Of 4 patients with a raised transferrin saturation level, 2 had raised serum ferritin levels and hemochromatosis, 1 had raised serum ferritin and hemosiderosis on liver biopsy, and 1 had a normal transferrin saturation level on repeat testing. Two of 3 cases of hemochromatosis had other clinical markers of the condition. Therefore, routine screening of diabetic patients for hemochromatosis is not necessary, because patients with hemochromatosis will often have other clinical features of the disease. When screening diabetic patients for hemochromatosis, it should be remembered that a persistently raised serum ferritin level has a low positive predictive value (16.6%) and that a normal transferrin saturation level does not exclude the diagnosis.
Total Serum Glycosylated Proteins in Detection and Monitoring of Gestational Diabetes
Authors: Cefalu William T , Prather Kaye L , Chester Donna L , Wheeler Catherine J , Biswas Manoj , Pernod Martin L
Published: March 2007

The goal of this study was to determine whether serum glycosylated protein levels (i.e., fructosamine) can reliably screen for gestational diabetes and whether these levels are valid markers of short-term glycemic control in the third trimester of pregnancy. Ninety-seven pregnant women at 26–28 wk gestation were evaluated over 9 mo. HbA1c and serum glycosylated protein (serum fructosamine) were determined at the baseline venipuncture of the 100-g oral glucose tolerance test performed to detect gestational diabetes. Of the 97 women studied, 13 tested positive for gestational diabetes (National Diabetes Data Group criteria). There were significant differences in the fasting and 1-, 2-, and 3-h glucose values between nondiabetic and diabetic patients (P < 0.005 at each time point). No difference was noted in the baseline serum glycosylated protein level (2.02 ± 0.08 vs. 1.98 ± 0.02 mM, NS) or HbA1c level (4.42 ± 0.2 vs. 4.6 ± 0.3%, NS) between gestational and nondiabetic patients. Diabetic patients were followed at 2-wk intervals, with serum glycosylated protein analysis, HbA1c, fasting glucose, and mean glucose determined by outpatient monitoring. Serum glycosylated protein correlated significantly to fasting blood glucose (r = 0.81, P < 0.001) and mean outpatient glucose (r = 0.62, P < 0.001) at the 2-wk follow-up visits. No correlation was found between HbA1c and fasting blood glucose (r = 0.11, NS) or mean outpatient glucose (r = −0.12, NS) during the follow-up period. The serum glycosylated protein level (serum fructosamine) is not a useful screening test for gestational diabetes. However, this assay shows potential as an objective marker of short-term control in evaluating the maternal glycemic state.
Role of Diabetologist in Evaluating Diabetic Retinopathy
Authors: Nathan David M , Fogel Howard A , Godine John E , Lou Peter L , D'Amico Donald J , Regan Charles DJ , Topping Trexler M
Published: March 2007

objective

To evaluate the ability of diabetologists to screen diabetic patients for diabetic retinopathy.

Research Design and Methods

Comparison of eye examination performed by diabetologists with direct ophthalmoscopy through an undilated pupil and by ophthalmologists through a dilated pupil with seven-field stereoscopic fundus photography (gold standard). The study consisted of 67 insulin-dependent and non-insulin-dependent diabetic outpatients attending a diabetes clinic.

Results

On the basis of fundus photography, patients were classified as having no or insignificant (30%), minimal (31%), moderate (24%), or severe (15%) retinopathy. The diabetologists and ophthalmologists performed similarly in their ability to classify severity of diabetic retinopathy accurately. When no or insignificant retinopathy (isolated microaneurysms only) was detected by examination, clinically significant retinopathy detected by fundus photography was highly unlikely (< 5%). On the other hand, if more than isolated microaneurysms were seen on examination, all examiners missed more severe lesions detected by fundus photography. Patients with corrected visual acuity worse than 20/30 had a high likelihood (100%) of moderate or severe retinopathy.

Conclusions

Motivated well-trained diabetologists can screen for diabetic retinopathy. The absence of detectable lesions by direct ophthalmoscopy indicates that automatic referral to an ophthalmologist is not necessary. However, if any level of retinopathy is detected or corrected acuity is worse than 20/30, referral to an ophthalmologist is required. In this setting, fundus photography is advised because it is the most sensitive means of detecting clinically significant retinopathy. If other nonophthalmologists can be trained to achieve similar results, current recommendations for ophthalmologic referral that require annual ophthalmologic examinations for most diabetic patients may need to be reconsidered.
Link Between Hypertension and Diabetes Mellitus Epidemiological Study of Chinese Adults in Taiwan
Authors: Tai Tong-Yuan , Chuang Lee-Ming , Chen Chien-Jen , Lin Boniface J
Published: March 2007

Objective

To elucidate the relationship between hypertension and non-insulin-dependent diabetes.

Research Design and Methods

The study consisted of a random sample of adults aged ≥ 40 yr from the Ta-An district of Taipei City and 5 of 12 villages of Taiwan province, which had established primary health-care centers since 1984. A total of 11,478 subjects were recruited into the survey with a response rate of 65.3 and 72%, respectively. Blood glucose and blood pressure levels were measured, and a structured questionnaire was given to each participant. Those identified as having diabetes received further blood tests for lipids and creatinine and were evaluated for vascular complications.

Results

The age- and sex-adjusted prevalence of hypertension among diabetic subjects was twice that of nondiabetic subjects (30.6 vs. 16.4%, P < 0.0005). Hypertensive subjects had a higher prevalence of diabetes than normotensive subjects (10.2 vs. 4.9%, P < 0.0005). Among hypertensive subjects, the prevalence of diabetes was 12.7% for those taking antihypertensive drugs and 9.1% for those not taking any drug (P < 0.05). The prevalence of diabetes significantly increased as mean arterial pressure rose, whether the subjects were stratified by various factors. Multiple regression analysis, including sex, age, body mass index, and other risk factors as independent variables, also showed a significant association between diabetes and hypertension.

Conclusions

The univariate and multivariate analyses revealed that there seemed to be a tight link between hypertension and non-insulin-dependent diabetes. Family history of diabetes, diabetes duration, diabetes regimen, control of blood glucose, and the presence of nephropathy, as attested by proteinuria, did not contribute to the risk of hypertension. Further studies are necessary to determine whether these two conditions are causally related.
Relationship Between Habitual Physical Activity and Insulin Levels Among Nondiabetic Men and Women: San Luis Valley Diabetes Study
Authors: Regensteiner Judith G , Mayer Elizabeth J , Shetterly Susan M , Eckel Robert H , Haskell William L , Marshall Julie A , Baxter Judith , Hamman Richard F
Published: March 2007

Objective

To determine whether higher levels of physical activity would be associated with lower fasting insulin and C-peptide levels in a free-living nondiabetic population.

Research Design and Methods

A cross-sectional study was conducted with a Hispanic and non-Hispanic white population of 442 men and 489 women with normal glucose tolerance (by World Health Organization criteria) in two rural Colorado counties. Total physical activity was assessed by a 7-day physical activity recall from which metabolic equivalents were estimated. Relationships between metabolic equivalents and fasting insulin and C-peptide were assessed while considering obesity, age, and other risk factors known to influence fasting insulin levels.

Results

Among all subjects, univariate analyses showed that higher activity levels were associated with lower mean fasting insulin and C-peptide levels (P < or equal to 0.05). Multiple linear regression showed that higher activity was significantly associated with lower values of log fasting insulin and C-peptide levels in men only (P < 0.001) independent of obesity, fat distribution, and age. Men in the highest tertile of activity had an adjusted mean fasting insulin level of 59.2 pM and fasting C-peptide level of 0.5 nM compared with a fasting insulin level of 72.7 pM and fasting C-peptide level of 0.6 mM for men in the lowest tertile of activity. The magnitude of the inverse association between activity and insulin was greatest in older rather than younger men. Physical activity was not associated with fasting insulin or C-peptide levels in women in the multivariate analyses.

Conclusions

Based on cross-sectional data, we conclude that higher levels of habitual physical activity are associated with lower fasting insulin and C-peptide levels in Hispanic and non-Hispanic white men.
Skin Reactive Hyperemia in Diabetic Patients: A Study by Laser Doppler Flowmetry
Authors: Tur Ethel , Yosipovitch Gil , Bar-On Yael
Published: March 2007

Objective

To assess whether laser Doppler flowmetry could detect differences in the cutaneous response to postischemic reactive hyperemia between patients with non-insulin-dependent diabetes mellitus (NIDDM) and nondiabetic controls and among subgroups of NIDDM patients.

Research Design and Methods

We measured the cutaneous blood flow on the forearms during the postischemic reactive hyperemia test in diabetic patients and nondiabetic controls. Subjects were 25 patients with NIDDM from the outpatient clinics of dermatology, ophthalmology, and endocrinology and 25 nondiabetic volunteers matched for sex and age. Of the patients with NIDDM, 14 had proliferative retinopathy, and 13 were obese. Cutaneous postischemic reactive hyperemia test monitored by measuring the cutaneous blood flow with laser Doppler flowmetry was used. Peak blood flow (P) after arterial occlusion, the time required to reach this peak (Tp) and the ratio (K) between these two quantities (K = P/Tp) were measured.

Results

In diabetic patients, P was significantly lower (P < 0.02) than in nondiabetic control subjects. In diabetic patients with proliferative retinopathy, K was lower (P < 0.05) than in diabetic patients without retinopathy. Diabetic patients with a body mass index (BMI; wt/ht2) < 25 kg/m2 had a longer Tp (P < 0.002), whereas the control group BMI did not affect this parameter. The combination of retinopathy and BMI < 25 gave the longest Tp values (P < 0.0001).

Conclusions

Postischemic hyperemia tests in diabetic patients reveal cutaneous microcirculatory changes in the forearm (lower P). Advanced retinopathy is associated with functional disturbances (lower K), especially when combined with a low BMI (< 25; longer Tp).
Health, Life, and Automobile Insurance Characteristics in Adults With IDDM
Authors: Songer Thomas J , LaPorte Ronald E , Dorman Janice S , Orchard Trevor J , Becker Dorothy J , Drash Allan L
Published: March 2007

Objective

To determine whether people with insulindependent diabetes mellitus (IDDM) were compromised in their access to insurance.

Research Design and Methods

A case-control study of 158 people with IDDM and 158 nondiabetic siblings matched for age and sex was conducted to evaluate the health, life, and automobile insurance characteristics and history of people with IDDM.

Results

Health insurance coverage (yes/no) among the IDDM and sibling control subjects was similar. More than 90% of the IDDM and control respondents had insurance through a private third-party source, and this insurance did not differ by type of plan, coverage, or premium. However, Medicare coverage was more common among the IDDM subjects and was associated with the presence of severe diabetic complications. IDDM subjects were also more likely to have been denied a health insurance policy by an insurer than were the control subjects (23 vs. 1%, P < 0.001). Similarly, there was no difference between the IDDM and sibling control subjects in the number who had a life or automobile insurance policy. However, life and automobile insurance refusal was much more frequent among the IDDM respondents, more so for life (55 vs. 0%, P < 0.001) than for automobile (12 vs. 4%, P < 0.05) insurance.

Conclusions

These results suggest that access to insurance is severely compromised for people with IDDM. Although most of those with IDDM are able to find some form of insurance, it is evident that on average they must go to extra lengths to find it. These data and a changing insurance environmentemphasize the need to reexamine, as a society, the importance of insurance for people with chronic disease, particularly IDDM.