bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Physical Fitness and Glycemic Control on In Vivo Insulin Action in Adolescents With IDDM
Authors: Arslanian Silva , Nixon Patricia A , Becker Dorothy , Drash Allan L
Published: March 2007

The relationship of in vivo insulin-mediated glucose utilization to the state of physical fitness and the degree of glycemic control was examined in 27 adolescents with insulin-dependent diabetes mellitus (IDDM) compared with 10 nondiabetic adolescent control subjects. In vivo total-body insulin-mediated glucose metabolism was evaluated by the hyperinsulinemic-euglycemic clamp. Physical fitness was assessed by maximal oxygen consumption (Vo2 max) during cycle ergometry. Patients and control subjects had similar levels of Vo2 max (34.9 ± 8.6 vs. 38.6 ± 9.9 ml · kg−1 · min−1, P = 0.3). Patients had lower total-body insulin-mediated glucose metabolism compared with control subjects (33.9 ± 14.3 vs. 63.8 ± 17.2 μmol · kg−1 · min−1, P = 0.0002). Among the patients, females had lower total-body insulin-mediated glucose metabolism compared with males (24.2 ± 2.8 vs. 40.7 ± 3.4 μmol · kg−1 · min−1, P < 0.001); however, this difference disappeared after correcting for sex differences in fitness levels. Insulin-mediated glucose metabolism correlated with Vo2 max in patients and control subjects (r = 0.83, r = 0.81, P < 0.05). The regression of total-body insulin-mediated glucose metabolism on Vo2 max for patients was −2.84 ± 0.255 Vo2 max and for control subjects was 7.12 ± 0.143 Vo2 max, indicating that for similar degrees of physical fitness patients have lower total body insulin-mediated glucose metabolism levels than control subjects. In patients, total-body insulin-mediated glucose metabolism correlated with the degree of glycemic control as assessed by the level of glycosylated hemoglobin (r = −0.63, P < 0.001). In a multiple regression analysis including Vo2 max and glycosylated hemoglobin, the coefficient of determination explaining the variation in total-body insulin-mediated glucose metabolism was 73%. It is concluded that adolescents with IDDM are insulin resistant compared with healthy control subjects, and this resistance is attributable to the state of diabetes control. However, the level of physical fitness explains a major part of interindividual variation in insulin action in both control subjects and adolescents with IDDM.
Randomized Crossover Study of Effect of Resistance Training on Glycemic Control, Muscular Strength, and Cholesterol in Type I Diabetic Men
Authors: Durak Eric P , Jovanovic-Peterson Lois , Peterson Charles M
Published: March 2007

The goal of this study was to evaluate a program of resistance weight training on cardiovascular risk factors, blood glucose management, and overallstrength in diabetic subjects. A randomized crossover design was performed on eight male type I (insulin-dependent) diabetic subjects (mean ± SD age 31 ± 3.5 yr, height 176 ± 5.6 cm, body wt 80 ± 15 kg, duration of diabetes 12.3 ± 9.8 yr, and insulin dose 24 U NPH/day and 21 U regular/day). The program consisted of heavy-resistance weight training 3 days/wk for 10 wk, concentrating on the strengthening of major muscle groups through progressive resistance. Blood tests included total cholesterol, triglycerides, very-low-density lipoprotein and high-densitylipoprotein cholesterol, and HbA1c. These tests were repeated atthree time points during the program. Field-strength testing was performed before and after training. An improvement was seen in the squat (93.6% increase, P < 0.0001) and bench press (58% increase, P < 0.005). HbA1c and triglyceride levels showed no change during the resting portion ofthe experiment but showed a significant change with the training program: HbA1c 6.9 ± 1 . 4 vs. 5.8 ± 0.9% (P = 0.05) and triglyceride 5.044 ± 1.06 vs. 4.628 ± 0.88 mM (P = 0.01). Self-monitored glucose (taken pre- and postexercise) showed a decrease from 7.85 ± 3.13 to 7.05 ± 2.91 mM (P = 0.0001). Very-low-density lipoprotein cholesterol and triglycerides did not change after training. Analysis of variance showed no significant differences over time from the three time points with regard to reductions in cardiovascular risk factors or HbA1c. Heavy-resistance strength training may be associated with a decrease inglycosylated hemoglobin and cholesterol in type I diabetic men after training, in addition to increasing overall strength.
Comparison of Quantitative Sensory-Threshold Measures for Their Association With Foot Ulceration in Diabetic Patients
Authors: Sosenko Jay M , Kato Marta , Soto Ramon , Bild Diane E
Published: March 2007

We compared the accuracy of cutaneous pressure perception-threshold measurements with that of other sensory-threshold measurements for detecting diabetic foot ulcer patients. Three hundred fourteen non-insulindependent diabetic patients were studied, of whom 91 had either a current foot ulcer or a history of foot ulceration. Foot ulcer patients had much higher pressure perception thresholds at the hallux than those without foot ulcers (mean ± SE 4.63 ± 0.05 vs. 3.54 ± 0.04 U, P < 0.001). The magnitude of association was higher than that for vibration thresholds and markedlygreater than those for cool and warm thresholds. Pressure thresholds were highly accurate for identifying foot ulcer patients. At a threshold level of 4.21 U, the sensitivity was 0.84, with a specificity of 0.96. At similar sensitivities for vibration and thermal thresholds, specificities were lower. Foot ulceration and cutaneous pressure perception threshold are strongly associated. Pressure-threshold measurements are extremely accurate and perform atleast as well as other quantitative sensory tests in identifying foot ulcer patients. Assessment of the foot pressure threshold may have promise as a simple and inexpensive method for detecting diabetic patients at risk for footulcers.
WHO Multinational Project for Childhood Diabetes
Authors:   WHO Diamond Project Group
Published: March 2007

Insulin-dependent diabetes mellitus (IDDM) is one of the most important chronic diseases of children worldwide. IDDM leads to an 8- to 10-fold excess risk of mortality in developed countries, whereas in developing countries,most cases die within a few years. A 60-fold international gradient in IDDM incidence has been reported, and epidemic periods have been identified. A new World Health Organization program, Multinational Project for Childhood Diabetes (Diabetes Mondiale or DIAMOND), has been developed to investigate and characterize global incidence, mortality, and health care. Over 10 yr (1990–1999), this study will collect population-based data concerning IDDM in >90 centers in 50 countries worldwide. The goals of DIAMOND are to collect standard information on incidence, risk factors, and mortality associated withIDDM; evaluate the efficiency and effectiveness of health care and the economics of diabetes; and establish national and international training programsin diabetes epidemiology. It is hoped that the DIAMOND project will be instrumental for the prevention of this serious disease and its sequelae.
Lack of Effect of Clonidine and Pentoxifylline in Short-Term Therapy of Diabetic Peripheral Neuropathy
Authors: Cohen Kenneth L , Lucibello Francine E , Chomiak MaryAnn
Published: March 2007

The goal of this study was to confirm or rule out anecdotal reports of beneficial effects of clonidine and pentoxifylline in the treatment of painful diabetic peripheral neuropathy. Clonidine was administered to 16 subjects at two dosage levels (0.1 and 0.2 mg/day) and was compared to placebo ina crossover design, with each phase lasting 4 wk. Either pentoxifylline (400mg 3 times/day) or placebo was given to 21 subjects in a 12-wk trial. Discomfort was characterized and rated with a subjective pain score (range 0–20). There was a significant decrease in pain score from baseline with both active drugs (P < 0.05), but this was no better than the response to placebo (P < 0.30 for clonidine and P < 0.95 for pentoxifylline). This study does not demonstrate a short-term benefit of either clonidine or pentoxifylline in the treatment of peripheral neuropathy.
Theoretical and Baseline Considerations for Diet and Weight Control of Diabetes Among Blacks
Authors: Kumanyika Shiriki K , Ewart Craig K
Published: March 2007

This article outlines theoretical considerations for diet and weight control of non-insulin-dependent diabetes mellitus (NIDDM) and identifies factors that may be of particular importance in influencing the success of diet and weight control of NIDDM in the Black population. Long-term adherence to dietary or weight-control regimens requires that the patient evaluate and restructure established eating and physical activity patterns. With the use of the social action theory as a conceptual framework, this complex behavioral change task can be understood as a function of the interplay of various self-regulatory mechanisms. These mechanisms are influenced by the person's capabilities for making changes, his'her physical condition and general health status, the physical and social environmental context, and the person's material and social resources. Many of these factors may differ for Blacks and Whites in a direction that suggests a lesser potential for effective diet and weight-loss therapy among Black NIDDM patients. For example, compared with Whites, Blacks are more likely to have limited incomes, low educational attainment, ambivalence about weight control, multiple health problems, and high-fat high-sodium low-fiber diets or food preferences. However, some evidence suggests that state-of-the-art counseling approaches can be as effective for Blacks as for Whites. The challenge is to adapt the types of approaches suggested by the social action theory for culturally appropriate and costeffective delivery in Black community health-care settings.
Vocational Adjustment and General Well-Being of Young Adults With IDDM
Authors: Tebbi Cameron K , Bromberg Clifford , Sills Irene , Cukierman Jack , Piedmonte Marion
Published: March 2007

The vocational experiences and general well-being of 58 young adult subjects (mean age 24.3 yr) with insulindependent diabetes mellitus (IDDM) diagnosed during their adolescence were compared with that of 55 healthy matched control subjects with linear logistic discriminant function analyses. Assessment measures included the Rand General Well-Being Scale and the Rand Functional Limitations and Physical Abilities Batteries. Diabetic subjects, on average, reported significantly lower general well-being than control subjects, particularly in terms of health-related fears and feelings of depression. However, diabetic subjects did not report a pervasive functional deficit relative to control subjects and experienced similar employment rates and problems in the workplace. These results suggest that this group of young adult diabetic subjects has adjusted well to the demands of the workplace despite lower reports of general well-being. The results are discussed in light of relevant sampling issues.
Regulating Insulin-Receptor-Gene Expression by Differentiation and Hormones
Authors: Mamula P W , McDonald A R , Brunetti A , Okabayashi Y , Wong K Y , Maddux B A , Logsdon C , Goldfine I D
Published: March 2007

Insulin regulates cell function by first binding to the insulin receptor (IR) localized on the cell surface. With the cloning of IR cDNA and the IR-gene promoter, the regulation of the IR gene during differentiation and by various hormones can be studied. Muscle is a major target tissue for insulin action. BC3H1 cells, a mouse muscle cell line in culture, are a model cell type for studying insulin action. Differentiation in these cells results in a 5- to 10-fold increase in IR binding and a 5- to 10-fold increase in IR content. Studies of IR mRNA by Northern and slot-blot analyses reveal a 10-fold increase in IR mRNA after differentiation. These studies indicate that there is a selective increase in IR-gene expression during muscle differentiation. A similar increase in IRgene expression is observed for the IR during pancreatic acinar cell differentiation. Glucocorticoids increase IR content in several target tissues. Studies in cultured IM-9 lymphocytes indicate that glucocorticoids induce a 5-fold increase in IR mRNA levels. Studies of IR mRNA half-life indicate that glucocorticoids do not alter IR mRNA stability. When the transcription of the IR is measured by elongation assays, glucocorticoids directly stimulate IR transcription 5- to 10-fold. The effect is detectable within 30 min of glucocorticoid treatment and is maximal within 2 h. Therefore, these studies demonstrate that the IR gene is under the direct regulation of glucocorticoids. Insulin downregulates the IR in various target tissues. Prior studies indicate that this downregulation was partly because of accelerated IR degradation. Studying AR42J pancreatic acinar cells, we also found that insulin accelerates IR degradation. Moreover, in these cells, insulin decreases IR biosynthesis by ∼50%. Studies of IR mRNA indicate there is a concomitant decrease in IR mRNA levels after insulin treatment. Thus, insulin decreases IR-gene expression. The genomic structure of the IR promoter has been elucidated. Primer extension and nuclease S, analysis indicate that IR mRNA has multiple start sites. The promoter fragment was ligated to a promoterless “reporter” plasmid containing the bacterial gene chloramphenicol acetyltransferase (CAT). When this plasmid is transfected into cultured cells, CAT activity is detected, indicating promoter activity. Various portions of a genomic fragment were ligated to a promoter to study glucocorticoid regulation of the IR promoter. These studies indicate that IR-gene expression is regulated by differentiation and hormonal agents. Differentiation in muscle and acinar pancreas is associated with an increase in IRmRNA. When differentiated cells are studied, glucocorticoids upregulate IR-gene expression, whereas insulin downregulates this function.
Ion Channels and Insulin Secretion
Authors: Rajan Arun S , Aguilar-Bryan Lydia , Nelson Daniel A , Yaney Gordon C , Hsu Walter H , Kunze Diana L , Boyd A E
Published: March 2007

We review the role of ion channels in regulating insulin secretion from pancreatic β-cells. By controlling ion permeability, ion channels at the membrane play a major role in regulating both electrical activity and signal transduction in the β-cell. A proximal step in the cascade of events required for stimulus-secretion coupling is the closure of ATP-sensitive K+ channels, resulting in cell depolarization. Of particular relevance is the finding that this channel is directly regulated by a metabolite of glucose, which is the primary insulin secretagogue. In addition, this channel, or a closely associated protein, contains the sulfonylurea-binding site. Another K+ channel, the Ca2+-activated K+ channel, may be involved in cell repolarization to create homeostasis. Voltage-dependent Ca2+ channels are activated by cell depolarization and regulate Ca2+ influx into the cell. By controlling cytosolic free-Ca2+ levels ([Ca2+]i), these channels play an important role in transducing the initial stimulus to the effector systems that modulate insulin secretion. The link between a rise in [Ca2+[(and the terminal event of exocytosis is the least-understood aspect of stimulus-secretion coupling. However, phosphorylation studies have identified substrate proteins that may correspond to those involved in smooth muscle contraction, suggesting an analogy in the processes of stimulus secretion and excitation contraction. The advent of new methodology, particulary the patch-clamp technique, has fostered a more detailed characterization of the β-cell ion channels. Furthermore, biochemical and molecular approaches developed for the structural analysis of ion channels in other tissues can now be applied to the isolation and characterization of the β-cell ion channels. This is of particular significance because there appear to be tissue-specific variations in the different types of ion channels. Given the importance of ion channels in cell physiology, a knowledge of the structure and properties of these channels in the β-cell is required for understanding the abnormalities of insulin secretion that occur in non-insulin-dependent diabetes mellitus. Ultimately, these studies should also provide new therapeutic approaches to the treatment of this disease.
Feasibility of Adjustment of Insulin Dose by Insulin-Requiring Type II Diabetic Patients
Authors: Floyd John C , Funnell Martha M , Kazi Imtiaz , Templeton Carolyn
Published: March 2007

Type II (non-insulin-dependent) diabetes accounts for most of the diabetes morbidity and expense, yet no systematic study of the effects of intensification of treatment by such patients who require insulin treatment has been conducted. Therefore, patients were recruited from our diabetes clinics, and by random assignment, experimental and control groups were created (n = 26 and 27, respectively) that were not different at 0 mo regarding 20 demographic, physiological, and treatment variables. Experimental patients practiced an algorithm for adjustment of insulin dosage based on daily prebreakfast capillary blood glucose (CBG) measurements and any symptomatic hypoglycemia. At 2-, 4-, and 6-mo visits, records of CBG measurements were available to the physicians (n = 7), who changed insulin dosages of both groups ad libitum. Feasibility of the experimental treatment is evidenced by study completion by 87% of enrollers, monitoring on 88% of days, accuracy of CBG recording (recorded as percentage of memory meter value, 100.8), weight gain not exceeding that of control subjects, practice of treatment algorithm to effect changes in insulin dosage, modest increase in frequency of mild insulin reactions, and a decrease of glycosylated hemoglobin into the normal range.
Development of Questionnaire to Examine Relationship of Physical Activity and Diabetes in Pima Indians
Authors: Kriska Andrea M , Knowler William C , LaPorte Ronald E , Drash Allan L , Wing Rena R , Blair Steven N , Bennett Peter H , Kuller Lewis H
Published: March 2007

There was a need to design a questionnaire that could accurately assess the activity patterns of Native Americans to evaluate the relationship between physical activity and diabetes. Such a questionnaire was developed and implemented into the data collection scheme of the prospective Pima Indian Study of Arizona. The questionnaire, which assesses historical, past-year, and past-week leisure and occupational activity, was examined in 29 Pima individuals aged 21–36 yr and was shown to be reliable with test-retest correlations (rank-order correlations ranged from 0.62 to 0.96 for leisure and occupational activity). Reproducibility of the past-year leisure physical-activity estimate was determined in 69 participants aged 10-59 yr and was found to be reliable in all age-groups with the exception of the 10- to 14-yr-old age-group (rank-order correlations were 0.31 in the 10- to 14-yr-old age-group compared to 0.88 to 0.92 in those >20 yr of age). Validity of the current-activity section of the questionnaire was demonstrated indirectly through comparisons with activity monitors. The past-week leisure-activity estimate was related to the Caltrac activity monitor counts per hour (p = 0.62, P > 0.05, n = 17). In summary, a physical-activity questionnaire has been developed that is both reliable and feasible to use in the Pima Indian population to evaluate the relationship of physical activity to non-insulin-dependent diabetes mellitus.
Cigarette Smoking and Neuropathy in Diabetic Patients
Authors: Mitchell Braxton D , Hawthorne Victor M , Vinik Aaron I
Published: March 2007

We studied whether lifetime cigarette smoking is associated with the presence of diabetic neuropathy. The research design consisted of a case-control study conducted from a referral-based diabetes clinic at a major medical center. The patients were a 65% sample (163 insulin-dependent diabetes mellitus [IDDM] and 166 non-insulin-dependent diabetes mellitus [NIDDM] patients) of all patients admitted during a 26-mo period. Neuropathy was diagnosed on the basis of signs and symptoms. Smoking history was obtained by mailed questionnaire (66% response rate). Diabetes duration, HbA1, age, sex, peripheral vascular disease, hypertension history, and lifetime alcohol consumption were measured as covariates. The prevalence of neuropathy was 49 and 38% in IDDM (n = 113) and NIDDM (n = 104) patients, respectively. In IDDM, but not NIDDM, current or ex-smokers were significantly more likely to have neuropathy than individuals who had never smoked (odds ratio 2.46, P = 0.02), and the prevalence of neuropathy increased with increasing number of pack-years smoked (P < 0.001). After adjustment for covariates, IDDM patients smoking ≥30 pack-yr were 3.32 times more likely to have neuropathy than patients smoking less than this amount (95% confidence interval 1.15–9.58, P = 0.026). Cigarette smoking was associated with the presence of neuropathy in this clinic-based population of IDDM patients. The hypothesis that cigarette smoking is associated with diabetic neuropathy should be investigated further, both prospectively and in a more representative population.
Arterial Blood Pressure Related to Degree of Albuminuria and Low-Molecular-Weight Proteinuria in IDDM
Authors: Holm J , Hemmingsen L , Nielsen N V
Published: March 2007

Urinary excretion of albumin and retinol-binding protein (a marker of tubular proteinuria that results from impaired proximal tubular reabsorption of lowmolecular- weight proteins) was determined in 110 insulin-dependent diabetic (IDDM) subjects. A statistically significant correlation between the urinary excretion of both proteins, in particular the retinolbinding protein, and the height of arterial blood pressure (systolic and diastolic) was observed. Correlation was weak, i.e., factors other than incipient nephropathy could be of greater importance for the development of arterial hypertension in diabetes.
Clinical Significance of Erythrocyte Sorbitol—Blood Glucose Ratios in Type II Diabetes Mellitus
Authors: Aida Kaoru , Tawata Masato , Shindo Hideo , Onaya Toshimasa
Published: March 2007

The polyol pathway has been implicated in the pathogenesis of diabetic complications. To determine the activity of the polyol pathway, the ratio of erythrocyte sorbitol to blood glucose, which reflects aldose reductase activity, was evaluated in 329 patients with type II (non-insulin-dependent) diabetes mellitus and in 100 nondiabetic age-matched control subjects. Although erythrocyte sorbitol levels were markedly elevated, sorbitol-glucose ratios were significantly lower in diabetic patients than in nondiabetic subjects. Sorbitol-glucose ratios in diabetic patients decreased progressively as blood glucose and hemoglobin A1c (HbA1c) levels increased. Sorbitol-glucose ratios were also studied during a 75-g oral glucose tolerance test. Ratios were again lower in diabetic patients than those in nondiabetic subjects and significantly decreased 120 min after glucose loading. The ratio in diabetic patients also fell with increasing age of the patients. In diabetic patients with neuropathy, retinopathy, or nephropathy, however, sorbitol-glucose ratios were significantly higher than in those without these complications; ratios increased further as complications became more severe. Our findings suggest that the affinity of aldose reductase for glucose in patients with diabetic complications may be increased and that the polyol pathway is implicated in the pathogenesis of diabetic complications.
Development of Stable Film Test for Rapid Estimation of Blood or Plasma 3-Hydroxybutyrate
Authors: Harano Yutaka , Aoki Takahiko , Nakajima Yuzuru , Kojima Hideto , Kosugi Keisuke , Harano Aki , Hidaka Hideki , Yamada Shigeki , Uno Shizuo , Shigeta Yukio
Published: March 2007

A film test for the rapid detection of plasma/serum 3-hydroxybutyrate (3-OHB) has been developed. The film contains NAD, nitro blue tetrazolium, 3-OHB dehydrogenase, and diaphorase, and the surface is coated with modified biomembrane and can detect 50- 1500 μM 3-OHB within 2–3 min. One drop or 50 μl of plasma/serum or blood is applied to the film, and the violet color is read via reflectance meter after 2 min. Plasma/serum samples >1500 μM 3-OHB can be measured by dilution with saline. In blood with 40% hematocrit, the color developed is 50% less than with plasma/serum, and this was adjusted in the reflectance meter. A good correlation (r = 0.99) was observed between results with automated and film methods and between visual methods and reflectance meter. In insulin-dependent diabetes mellitus, all 3 subjects with positive ketonuria (+ +), 8 of 12 subjects with mild ketonuria (+), and 7 of 25 subjects without ketonuria exhibited elevation of 3-OHB in blood >200 μM. The results indicate that 3-OHB film is valuable not only in the emergency room for the differential diagnosis between ketoacidotic and nonketotic hyperosmolar coma but also as a marker for insulin dependency, energy dependency on fatty acid compared with glucose, and metabolic control of diabetes.
Combination Insulin-Sulfonylurea Therapy
Authors: Lebovitz Harold E , Pasmantier RoseMarie
Published: March 2007

Combination sulfonylurea-insulin therapy for patients with diabetes mellitus has been evaluated by numerous investigators with various experimental designs. Much of the data are conflicting, and clear conclusions do not seem justified. Insulin-sulfonylurea therapy is probably not clinically useful in most patients with insulindependent diabetes mellitus. Most non-insulindependent diabetic (NIDOM) patients are also unlikely to have meaningful improvement in glycemic regulation on insulin-sulfonylurea therapy. A subset of NIDDM patients who are mildly to moderately obese, have adequate endogenous insulin secretory reserve, and are in poor glycemic regulation (fasting plasma glucose >11mM and/or HbA1 >10%), despite twice-daily insulin administration of >70 U/day, may show significant improvement of glycemic regulation and/or decreases in insulin daily dose on insulin-sulfonylurea therapy. The mechanisms by which insulin-sulfonylurea therapy improves glycemic regulation and decreases insulin requirements involve an increase in endogenous insulin secretion and possibly some extrapancreatic actions of the sulfonylureas on muscle and liver.
Metabolic Response to Oral Challenge of Hydrogenated Starch Hydrolysate Versus Glucose In Diabetes
Authors: Wheeler Madelyn L , Fineberg S Edwin , Gibson Reid , Fineberg Naomi
Published: March 2007

Our objective was to determine whether 1) hydrogenated starch hydrolysates (HSHs), bulking/sweetening agents used in hard candies, produce a diminished postmeal glycemic response relative to glucose in individuals with and without diabetes and 2) any diminished glycemia is secondary to altered carbohydrate absorption. This study followed a randomized double-blind crossover design and was performed in 12 individuals with diabetes (6 non-insulin dependent, 6 insulin dependent) and 6 nondiabetic individuals. Each group consisted of 3 men and 3 women, none with known neuropathy. After an overnight fast, each subject was challenged with 50 g of glucose, HSH 5875 (7% sorbitol/60% maltitol), and HSH 6075 (14% sorbitol/78% hydrogenated maltooligosaccharides)/1.73 m2 of body surface area in random order on 3 successive days. Individuals with diabetes were maintained on continuous subcutaneous insulin infusion throughout the study to achieve prechallenge glucose levels between 4.5 and 6.7 mM. For all groups, the order of plasma glucose responses over 5 h postchallenge was glucose>HSH 6075>HSH 5875, P < 0.001 (glucose vs. HSH). Pooled data for all groups for areas under the curve confirmed that HSH 6075 resulted in greater glycemia than HSH 5875 (P < 0.05). This was reflected in the order of C-peptide responses seen in the nondiabetic and non-insulindependent groups (glucose>HSH 6075>HSH 5875, P < 0.001). Breath H2 after glucose was low, whereas HSH 5875 > HSH 6075 (P = 0.003). Gastric distress was noticed with all products. HSH ingestion as a single carbohydrate ingredient results in decreased glycemia relative to glucose in individuals with and without diabetes. Decreased glycemia results from altered small intestinal carbohydrate absorption. HSH as a single ingredient appears to be a suitable product for consumption by individuals with diabetes mellitus.
Autonomic Influence on Pregnancy Outcome in IDDM
Authors: Airaksinen KE Juhani , Anttila L Marjatta , Linnaluoto Markku K , Jouppila Pentti I , Takkunen Juha T , Salmela Pasi I
Published: March 2007

We evaluated the autonomic influence on pregnancy outcome with prospective study of 100 consecutive pregnancies in women with insulin-dependent diabetes mellitus (IDDM). Tests of cardiovascular autonomic nervous function were performed at the beginning of each pregnancy, and two groups were formed. Group 1 was comprised of 23 pregnancies with autonomic dysfunction, and group 2 was comprised of 77 pregnancies with no abnormalities in cardiovascular tests. Elective abortion was later induced for medical reasons in two cases in group 1, and these women were excluded from the study. The groups were comparable with respect to age, duration of diabetes, and presence of nephropathy. Both groups also achieved comparable glycemic control during pregnancy. There were no significant differences between groups 1 and 2 in any specific pregnancy complication (spontaneous abortions, 5 vs. 3%; perinatal mortality, 10 vs. 1%; congenital malformations, 10 vs. 4%; respiratory distress syndrome, 5 vs. 8%; preeclampsia, 20 vs. 10%; maternal ketoacidosis, 4 vs. 0%; and maternal hypoglycemic accidents, 10 vs. 4%, respectively), but the frequency of pregnancies with at least one of the above complications was greater in group 1 (52 vs. 23%, P = 0.01). Stepwise logistic regression analysis showed the association between autonomic dysfunction and pregnancy outcome to be independent of high initial glycosylated hemoglobin levels, long duration of diabetes, and nephropathy. Maternal autonomic dysfunction seems to be associated with an increased frequency of overall pregnancy complications but does not significantly interfere with the achievement of tight metabolic control during pregnancy.
Cyclosporin Therapy for Prevention and Cure of IDDM: Epidemiological Perspective of Benefits and Risks
Authors: Lipton Rebecca , LaPorte Ronald E , Becker Dorothy J , Dorman Janice S , Orchard Trevor J , Atchison Joycelyn , Drash Allan L
Published: March 2007

Cyclosporin and other immunosuppressive agents have been proposed as a preventive treatment against the development of insulin-dependent diabetes mellitus (IDDM) in relatives at increased risk for the disease, based on the understanding that its etiology is an ongoing process of autoimmune β-cell destruction. We used an epidemiological approach to evaluate several recent trials of cyclosporin in newly diagnosed IDDM patients to determine the degree of benefit that is to be expected. We assessed these and other studies to estimate the potential adverse effects of such treatment, were it to be used in the future, either in newly diagnosed subjects or healthy high-risk relatives. Standard sample-size calculations were used to quantify the number of study subjects necessary to allow adequate statistical power to test the positive and negative effects of a future treatment (α = 0.05, β = 0.20). The estimates were based on the data available from published studies of cyclosporin treatment. The importance of conducting an adequate trial of such a therapy, both from an ethical and a practical viewpoint, is discussed. Five small immunosuppression trials were evaluated. Remission rates in treated subjects exceeded those in control subjects by 15-59%. Variability in defining remission may account for the differences in rates across the studies. Estimates of the major beneficial and adverse effects of cyclosporin were derived from these trials and studies of patients who have undergone long-term immunosuppression. Indicators of kidney damage associated with cyclosporin treatment were reported in 5-47% of treated subjects. A threefold increase in the rate for all cancers and an eightfold increase in the rate for non-Hodgkin's lymphoma were reported in immunosuppressed autoimmune patients. To detect a beneficial effect such as that described for cyclosporin, between 14 and 2598 subjects would be required in a clinical trial. Samplesize calculations demonstrated that between 1200 and 156,000 subjects would need to be enrolled in such a trial to detect a twofold increase over baseline levels of the adverse effects reported in the studies reviewed herein. Of critical importance are not the specific findings concerning the risks and benefits of cyclosporin but rather the use of an epidemiological approach for evaluating any future immunosuppressive treatments designed to prevent or cure IDDM.
Exercise-Induced Hypertension in Normotensive Patients With NIDDM
Authors: Blake Gerald A , Levin Seymour R , Koyal Sankar N
Published: March 2007

The aim of this study was to determine whether blood pressure during mild to moderate exercise is abnormal in patients with non-insulin-dependent diabetes mellitus (NIDDM). The study group consisted of 11 patients with NIDDM and 11 nondiabetic subjects of comparable age and body mass index. All subjects were sedentary and basally normotensive. Bicycle ergometry was used to assess the effect of exercise on blood pressure at a steady state of 70–75 W, with a target duration of 20 min. Blood pressure was measured basally and every 5 min. Greater exercise-induced systolic blood pressure (mean max 208.0 ± 6.0 vs. 177.0 ± 3.0 mmHg) occurred in the NIDDM group (P < 0.001). Neither pulse rate nor diastolic blood pressure differed between the groups before or during exercise. Return to basal pulse and blood pressure was similar. Mild to moderate exercise induces greater systolic blood pressure in sedentary patients with NIDDM. Because exercise is recommended as one therapeutic modality, intraexercise blood pressure should be considered in assessing the safety of this form of treatment.
Influenza Infection and Diabetes Mellitus: Case for Annual Vaccination
Authors: Diepersloot Rob J A , Bouter Karel P , Hoekstra Joost B L
Published: March 2007

Herein, epidemiological data on influenza pneumonia and mortality, results of clinical studies, and the outcome of influenza vaccination trials are reviewed. All excess mortality studies that specify for underlying disease list diabetes as one of the major risk factors. During influenza epidemics, death rates among patients with diabetes mellitus may increase by 5–15%. Diabetes mellitus is also mentioned as a risk factor in most clinical studies, making up 3–14% of the patients studied. Even in recent studies, diabetes mellitus is only preceded as a risk factor by cardiovascular disease and chronic pulmonary disorders. To what extent cardiovascular disease and old age contribute to the increased influenza mortality and morbidity in diabetic patients remains unclear. The influence of epidemic influenza on the incidence ofdiabetic acidosis in combination with an impaired immune response to both Staphylococcus aureus and the influenza virus suggests that diabetes mellitus itself is the main risk factor. It is concluded that all patients with diabetes mellitus should receive annual vaccinations and that, in official recommendations, patients with diabetes mellitus should be mentioned as a separaterisk group. Wholevirus vaccines are preferred over subunit vaccines.
Mail-In Paper Strip vs. Microcolumn Technique for Measurement of Glycosylated Hemoglobin
Authors: Slemenda Charles W , Marrero David G , Fineberg S Edwin , Moore Patricia S , Gibson Reid
Published: March 2007

We compared glycosylated hemoglobin (GHb) determined from capillary blood samples on paper strips with a standard microcolumn technique in a crosssectional observational study with laboratories blinded to duplicate samples. Both the standard and the filter strip laboratories were provided with 80 uniquely identified blood samples from 40 individuals. Each laboratory ran duplicate analyses on each sample, yielding 160 GHb values. The within-laboratory correlations between blinded duplicates were 0.98 for the standard (microcolumn technique) and 0.94 for the filter paper (affinity technique) laboratories. The between-laboratory correlations ranged from 0.69 to 0.77. When classifying patients by quartile of glycemic control, the laboratories agreed on 60% of the patients. In an effort to identify sources of between-laboratory variability, varying quantities of blood were applied to strips and reanalyzed. Five microliter drops always yielded inflated estimates of GHb. These data suggest that the estimates of GHb obtained from mail-in paper strips, although internally consistent, differ in important ways from standard laboratory values, reemphasizing the need for caution in the interpretation of interlaboratory and intermethod comparisons.
Effect of Isocaloric Substitution of Chocolate Cake for Potato in Type I Diabetic Patients
Authors: Peters Anne L , Davidson Mayer B , Eisenberg Katharine
Published: March 2007

Traditional dietary advice given to people with diabetes includes eliminating simple sugars (primarily sucrose) from the diet. Many people have difficulty following this recommendation. Because patients with type I (insulindependent) diabetes do not need overall calorie restriction, there is no caloric reason to restrict sucrose. In this study, we looked at the effect of the isocaloric substitution of a piece of chocolate cake for a baked potato ina mixed meal to determine whether this would increase the blood glucose in patients with type I diabetes. The glucose response to a cake-added meal was significantly greater than to a standard meal. The glucose response was no different between a cake-substitution meal and a standard meal. The reproducibility studies showed no difference between repeated standard meals. The urinary glucose excretion was significantly greater after a cake-added meal butwas no different with the other pairs. There were no significant differencesin the counterregulatory hormone responses at baseline between any of the paired studies. In conclusion, patients with type I diabetes may substitute a sucrose-containing dessert for another carbohydrate in their diet without compromising their postprandial glucose response. These data suggest that a dessert exchange may be helpful and not harmful in the management of diabetic patients. There is an inherent variability (at least 16%) in an insulin-requiring patient's response to a meal, making self-monitoring of blood glucose and adjustment of insulin doses necessary to achieve near euglycemia.
Natural History of β-Cell Dysfunction in NIDDM
Authors: Leahy John L
Published: March 2007

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and β-cell dysfunction. This review focuses on the β-cell, what defects occur when and why. Two major anatomic observations have been made in NIDDM. The β-cell mass is mildly reduced, especially when obesity is taken into account. Also, amyloid deposits are frequently observed in the islets. It is unclear whether these changes are genetically mediated or result secondary to the loss of glucose homeostasis. Many studies have looked at some aspect of insulin secretion in NIDDM, and two types of distinct abnormalities have been described. Early on, there is a marked disruption in pulsatile insulin delivery, which is potentially an important contributor to the insulin resistance. It is unclear whether the loss of pulsatile delivery is acquired or genetically induced. Later, after glucose intolerance has started, several other secretory abnormalities develop coincident with loss of β-cell glucorecognition. The net result is further deterioration in timing of insulin delivery and postprandial hyperglycemia. A second important consequence of the glucose blindness is that the inherent compensatory β-cell mechanisms that guard against hyperglycemia are bypassed. We propose that the loss of glucose responsiveness is a direct result of an elevated glucose concentration (socalled glucotoxicity) and have generated substantial data in rat models that support this idea. The logical conclusion is that β-cell function in NIDDM can be maximized by achieving the best metabolic control possible.
Superiority of Radiobinding Assay Over ELISA for Detection of IAAs in Newly Diagnosed Type I Diabetic Children
Authors: Levy-Marchal Claire , Bridel Marie-Pascale , Sodoyez-Goffaux Françoise , Koch Michel , Tichet Jean , Czernichow Paul , Sodoyez Jean-Claude
Published: March 2007

Objective

Liquid- or solid-phase assays have been used for insulin autoantibody (IAA) determination, and the method of IAA measurement has not been standardized.

Research Design and Methods

IAAs were determined by radiobinding assay (RBA) and enzyme-linked immunosorbent assay (ELISA) in two large age-matched groups of nondiabetic and newly diagnosed insulin-dependent (type I) diabetic children.

Results

Positivity for IAA by RBA (≥ to nondiabetic mean + 3SD) was 2 of 178 (1.1%) and 55 of 173 (32%) in nondiabetic and diabetic children, respectively. Prevalence of IAA by RBA was significantly higher in the youngest age-group (63% between 0-4 yr). Positivity for IAA by ELISA was 1 of 178 (0.6%) and 8 of 169 (4.7%) in nondiabetic and diabetic children, respectively. Concordance rates between both assays were 0 of 3 (0%) in control subjects and 5 of 58 (8.6%) in diabetic children.

Conclusions

We conclude that RBA is more appropriate than ELISA for IAA detection at the onset of the disease. In addition, because available data suggest that IAAs detected by RBA only are high-affinity antibodies, it is tempting to speculate that IAAs reflect a mature immune reaction against endogenous insulin.
Vitamin E Reduction of Protein Glycosylation in Diabetes: New Prospect for Prevention of Diabetic Complications?
Authors: Ceriello Antonio , Giugliano Dario , Quatraro Antonio , Donzella Claudio , Dipalo Giovanni , Lefebvre Pierre J
Published: March 2007

Objective

This study evaluated the possibility of inhibiting protein glycosylation in vivo with vitamin E.

Research Design and Methods

Two groups of 10 insulin-requiring diabetic patients, matched for duration of disease and metabolic control, received daily vitamin E supplementation of 1200 and 600 mg, respectively, for 2 mo. A third group of 10 diabetic patients, matched for duration of disease and metabolic control, served as the control group and received placebo. Fasting plasma glucose, mean daily plasma glucose, fasting labile HbA1, and glycosylated proteins were measured in the basal state and after 1 and 2 mo of treatment. In addition, hyperglycemic clamp studies were performed in basal state and after 1 mo of vitamin E administration in all patients.

Results

Glycemic indices did not show any significant changes during the study, whereas fasting labile HbA, and glycosylated proteins decreased significantly after 1 and 2 mo in patients on vitamin E administration. Stable HbA1 decreased after 2 mo. Mean glycemic incremental area in the hyperglycemic clamp procedure was similar before and after treatment, whereas a significant reduction in mean labile HbA1 incremental area was found after vitamin E supplementation. A significant difference was also found in both fasting and incremental labile HbA1 levels, stable HbA1, and glycosylated proteins between the two groups of diabetic patients on the two doses of vitamin E; the diabetic patients who received the higher dose of vitamin E showed the greater reduction. No significant changes in these parameters were observed in diabetic patients on placebo administration.

Conclusions

These results demonstrate that vitamin E administration may reduce protein glycosylation in diabetic subjects independently of changes in plasma glucose, an effect that may be due to the inhibition of labile glycosylation, the first step of the Maillard reaction. Long-term studies will help establish the usefulness of vitamin E administration for the prevention of diabetic complications.
Age-Related Differences in Case-Fatality Rates Among Diabetic Patients With Myocardial Infarction: Findings from National Hospital Discharge Survey, 1979–1987
Authors: Cooper Richard S , Pacold Ivan V , Ford Earl S
Published: March 2007

Objective

To determine age-related differences in case-fatality rates among diabetic patients with myocardial infarction (MI). Published studies have demonstrated 60% higher case-fatality rates during acute MI among diabetic patients compared with those without diabetes. However, many previous reports have been of insufficient size to examine the effect of age on mortality and have not been drawn from a representative sample of hospitals. The National Hospital Discharge Survey provides data on discharge diagnosis and vital status from a random sample of ∼ 500 short-stay American hospitals.

Research Design and Methods

In this analysis, people with acute MI listed as the first diagnosis on the discharge sheet were studied. Any mention of diabetes mellitus on the discharge sheet was used to stratify the patients into those with and without diabetes.

Results

Age-adjusted case-fatality rates were identical in patients with and without diabetes for both sexes: 16.1 vs. 16.3 in men and 18 vs. 18.2 in women, respectively. Mortality rates were, however, higher among the younger patients with diabetes. Ratios of the case-fatality percentage by 10-yr age-groups (age 35-75 yr) and ≤ 75 yr old for diabetes versus no diabetes were 1.7, 1.8, 1.2, 0.9, and 0.9 for men and 2.4, 1.2, 1.1, 1, and 0.9 for women.

Conclusions

Diabetes thus appears to increase the in-hospital mortality risk with acute MI disproportionately in the younger age-groups, particularly among men, and does not appear to be a marker of increased risk among the elderly.
Severe Amnesia After Hypoglycemia: Clinical, Psychometric, and Magnetic Resonance Imaging Correlations
Authors: Chalmers John , Risk Margaret T A , Kean David M , Grant Robin , Ashworth Bryan , Campbell Ian W
Published: March 2007

Objective

To determine the correlation between clinical, psychometric, and magnetic resonance imaging (MRI) findings after an episode of hypoglycemic coma resulting in amnesia.

Research Design and Methods

Detailed psychometric assessment, especially memory testing, performed with MRI in a man with severe amnesia after hypoglycemic coma.

Results

Psychometric testing confirmed impaired immediate recall. MRI findings were consistent with a lesion in the left temporal lobe.

Conclusions

This is the first description of MRI in determining the neurological damage in hypoglycemic coma.
Intra-Arterial Urokinase Infusion in Diabetic Patients With Rapidly Progressive Ischemic Foot Lesions
Authors: Vannini Pietro , Ciavarella Adolfo , Mustacchio Anna , Rossi Cristina
Published: March 2007

Objective

The effectiveness of local intra-arterial thrombolysis by urokinase was evaluated in eight non-insulin-dependent diabetic patients with angiographic evidence of infrapopliteal occlusive disease and rapidly progressive foot lesions.

Research Design and Methods

With an electric peristaltic pump, urokinase was infused for 96 h by a 5-6 F catheter introduced into the femoral artery and placed immediately above the occluded infrapopliteal arteries. After baseline, angiography was repeated at 24- to 48-h intervals and at conclusion of the treatment.

Results

Six patients showed immediate improvement of clinical symptoms. Angiography revealed the reestablishment of blood flow in collateral vessels of the leg and foot in the dorsal pedal artery in three patients and in the plantar arch in two. Recanalization of the major arteries of the trifurcation was not achieved. After 12 mo of follow-up, all limbs were salvaged, although four patients required vascular reconstruction to further improve foot perfusion and complete healing.

Conclusions

Intra-arterial urokinase, which opens collateral and smaller vessels of the leg and foot in patients with diabetes, may be effective in improving blood flow in lower extremities and in making the patient a better candidate for vascular surgery.