bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin Underdelivery From Implanted Pumps Using Peritoneal Route: Determinant role of insulin pump compatibility
Authors: Renard Eric , Bouteleau Serge , Jacques-Apostol Dominique , Lauton Dominique , Gibert-Boulet Françoise , Costalat Guy , Bringer Jacques , Jaffiol Claude
Published: March 2007

OBJECTIVE

To evaluate the incidence and investigate determinants of insulin underdelivery events occurring with implanted pumps using peritoneal route from a 103 patient-year experiment.

RESEARCH DESIGN AND METHODS

Of the MiniMed (MIP 2001) pumps implanted in 47 type I diabetic patients, 70 were refilled quarterly with four successive batches (A, B, C, D) of U400 Hoechst 21 PH neutral insulin during a 3-year study period. Any reduction of insulin flow rate >15% was considered as abnormal insulin delivery. Diagnosis of the cause of underdelivery was established according to the response to the following steps: 1) 0.01 mol/l NaOH rinse of pump circuits to solubilize insulin aggregates, 2) surgical examination and replacement of blocked catheters, and 3) postsurgical 0.01 mol/l NaOH rinse of pump. Step 2 was selected first if the increase of insulin requirements or reduction of flow rate were > 50%. Relative contributions of insulin and the implanted system to underdelivery events were analyzed.

RESULTS

There were 76 episodes of insulin underdelivery that occurred during the study, resulting in an incidence of 74 events per 100 patient-years. Of 52 NaOH pump rinses, 30 restored normal flow rate. Surgery, performed after rinse failure (n = 22) or as the first step (n = 24), disclosed catheter blockages due to tip obstructions in 28 cases and omental encapsulations in 18 other cases. Five combined severe reductions of pump flow rate requiring pump replacements were diagnosed during surgery, and additional NaOH rinses had to be performed after catheter change in 12 other cases. Analysis of the incidence of underdelivery events indicated that both pump- and catheter-related problems were significantly increased while implanted systems infused batches B, C, and D versus batch A (P < 0.01), whereas the duration of pump implantation had no significant influence.

CONCLUSIONS

Underdelivery events constitute serious limiting obstacles to prolonged peritoneal insulin infusion from implanted pumps. Progress in insulin pump compatibility is expected to reduce their occurrence and, thus, to improve the feasibility of this treatment.
Reducing Dynamic Foot Pressures in High-Risk Diabetic Subjects With Foot Ulcerations: A comparison of treatments
Authors: Lavery Lawrence A , Vela Steven A , Lavery David C , Quebedeaux Terri L
Published: March 2007

OBJECTIVE

To compare the effectiveness of total contact casts, commercially available therapeutic shoes, and removable walking casts to reduce mean peak plantar foot pressures at the site of neuropathic ulcerations in diabetic subjects.

RESEARCH DESIGN AND METHODS

We compared the reduction in peak plantar pressures at ulcer sites under the great toe (n = 5), first metatarsal (n = 10), and second through fifth metatarsals (n = 10) using six treatments: total contact casts (TCCs), DH Pressure Relief Walkers (DH), Aircast Pneumatic Walkers, Three D Dura-Steppers (3D), CAM Walkers, and P.W. Minor Xtra Depth shoes. A rubber sole canvas oxford was used to establish baseline pressure values. The canvas oxford could be viewed as a worse-case scenario for this patient population. With the EMED Pedar in-shoe pressure measurement system, data for 40 steps were collected for each treatment. We used Tukey's Studentized Range Test for simultaneous multiple comparisons to compare treatments.

RESULTS

DH Pressure Relief Walkers reduced plantar pressures significantly better than other commercially available treatments for ulcers under the first metatarsal, second through fifth metatarsals, and great toe (P < 0.05). There was not a significant difference in mean peak plantar pressures between TCCs and DHs at any of the forefoot ulcer sites.

CONCLUSIONS

DH Pressure Relief Walkers were as effective as total contact casts to reduce foot pressures at ulcer sites and may be an effective practical addition in the treatment of foot ulcers.
Glucagon-Like Peptide I Enhances the Insulinotropic Effect of Glibenclamide in NIDDM Patients and in the Perfused Rat Pancreas
Authors: Gutniak Mark K , Juntti-Berggren Lisa , Hellström Per M , Guenifi Amel , Holst Jens J , Efendic Suad
Published: March 2007

OBJECTIVE

To investigate the acute effects of glibenclamide and glucagon-like peptide I (GLP-I) and their combination in perfused isolated rat pancreas and in patients with secondary failure to sulfonylureas.

RESEARCH DESIGN AND METHODS

Rat islets were perfused with 10 nmol/l GLP-I in combination with 2 μumol/l glibenclamide. In human experiments, GLP-I (0.75 pmol. kg−1 · min−1) was given as a continuous infusion during 240 min, while glibenclamide (3.5 mg) was administered orally. Eight patients participated in the study (age 57.6 ± 2.7 years, BMI 28.7 ± 1.5 kg/m2, mean ± SE). In all subjects, blood glucose was first normalized by insulin infusion administered by an artificial pancreas (Biostator).

RESULTS

GLP-I increased the insulinotropic effect of glibenclamide fourfold in the perfused rat pancreas. In human experiments, treatment with GLP-I alone and in combination with glibenclamide significantly decreased basal glucose levels (5.1 ± 0.4 and 4.5 ± 0.1 vs. 6.0 ± 0.3 mmol/l, P < 0.01), while with only glibenclamide, glucose concentrations remained unchanged. GLP-I markedly decreased total integrated glucose response to the meal (353 ± 60 vs. 724 ± 91 mmol μ l−1 · min−1, area under the curve [AUC] [–30–180 min], P < 0.02), whereas glibenclamide had no effect (598 ± 101 mmol · l−1 · min−1, AUC [–30–180 min], NS). The combined treatment further enhanced the glucose lowering effect of GLP-I (138 ± 24 mmol · l−1 · min, AUC [–30–180 min], P < 0.001). GLP-I, glibenclamide, and combined treat-stimulated meal-induced insulin release as reflected by insulinogenic indexes (control 1.44 ± 0.4; GLP-I 6.3 ± 1.6, P < 0.01; glibenclamide 6.8 ± 2.1, P < 0.01; combination 20.7 ± 5.0, P < 0.001). GLP-I inhibited basal but not postprandial glucagon responses. Using paracetamol as a marker for gastric emptying rate of the test meal, treatment with GLP-I decreased gastric emptying at 180 min by ∼50% compared with the control subjects (P < 0.01).

CONCLUSIONS

In acute experiments on overweight patients with NIDDM, GLP-I exerted a marked antidiabetogenic action on the basal and postprandial state. The peptide stimulated insulin, suppressed basal glucagon release, and prolonged gastric emptying. The glucose-lowering effect of GLP-I was further enhanced by glibenclamide. This action may be at least partially accounted for by a synergistic effect of these two compounds on insulin release. Glibenclamide per se enhanced postprandial but not basal insulin release and exerted a less pronounced antidiabetogenic effect compared with GLP-I.
Evidence of a Relationship Between Childhood-Onset Type I Diabetes and Low Groundwater Concentration of Zinc
Authors: Haglund Bengt , Ryckenberg Katarina , Selinus Olle , Dahlquist Gisela
Published: March 2007

OBJECTIVE

Zinc deficiency has shown to increase the risk for diabetes in diabetes-prone experimental animals. Low concentrations of zinc have also been shown in serum of recent onset cases with IDDM. The present study examines the hypothesis that exposure to a low concentration of zinc in drinking water could increase the risk for future onset of IDDM.

RESEARCH DESIGN AND METHODS

Using the Swedish childhood diabetes registry and data on residence 3 years before the onset of disease, a case-control study was designed comparing cases and control subjects with estimates of groundwater contents of zinc obtained in biogeochemical samples from areas of residence.

RESULTS

A high groundwater concentration of zinc was associated with a significant decrease in risk (odds ration [OR] = 0.8; 95% CI = 0.7–0.9). The same OR was obtained when the model included information of other metals that might act as possible confounders (chromium, vanadium, cobalt selenium, cadmium, lead, and mercury). In small rural areas, in which drinking water is taken from local wells and thus is closely associated with the groundwater content within the area, an even stronger association between zinc and diabetes (OR = 0.6; 95% CI = 0.4–0.9) was found.

CONCLUSIONS

It is concluded that this study for the first time provides evidence that a low groundwater content of zinc, which may reflect long-term exposure through drinking water, is associated with later development of childhood onset diabetes.
The Effect of Glipizide Gastrointestinal Therapeutic System on Islet Cell Hormonal Responses to a Test Meal in NIDDM
Authors: Mooradian Arshag D , Albert Stewart G , Bernbaum Marla , Plummer Sharon
Published: March 2007

OBJECTIVE

To determine whether the abnormal glucagon and amylin secretions in NIDDM are secondary to hyperglycemia and relative hypoinsulinemia.

RESEARCH DESIGN AND METHODS

A total of 13 patients with NIDDM were studied before and after treatment with glipizide gastrointestinal therapeutic system (GITS) in a randomized double-blind placebo-controlled fashion. Of the 13 subjects, 9 were randomized to the glipizide GITS arm and 4 were randomized to the placebo arm of the study. Serum glucose, insulin, C-peptide, plasma glucagon, and plasma amylin concentrations were measured under fasting and postprandial (post-Sustacal ingestion) conditions. The Sustacal challenge was performed at baseline and after 12 weeks of treatment with either glipizide GITS or placebo.

RESULTS

Glipizide GITS treatment resulted in a significant reduction in hyperglycemia and increases in insulin and C-peptide secretion. Hyperglucagonemia was not ameliorated, and amylin secretion was not altered after glipizide GITS treatment. Placebo-treated patients did not show significant changes in any of the parameters measured.

CONCLUSIONS

Glipizide GITS treatment failed to ameliorate the hyperglucagonemia of NIDDM and did not alter amylin secretion even though it increased insulin secretion and significantly ameliorated the hyperglycemia. These observations suggest that NIDDM related abnormalities in some of the islet cell hormonal responses are the result of changes inherent in the islet cells and may be independent of hyperglycemia and relative hypoinsulinemia.
Incidence of Lower Limb Amputations and Diabetes
Authors: Trautner Christoph , Haastert Burkhard , Giani Guido , Berger Michael
Published: March 2007

OBJECTIVE

We collected data on the incidence rates of amputations and their relative risk in diabetic subjects compared with the nondiabetic population.

RESEARCH DESIGN AND METHODS

From all three hospitals in a city of ∼ 160,000 inhabitants, we obtained complete lists of nontraumatic lower limb amputations. From each patient record, diabetic status was determined. We estimated age-specific and standardized incidence rates of amputations in the diabetic and nondiabetic populations and in the entire population, as well as the relative and attributable risks due to diabetes.

RESULTS

Nontraumatic lower limb amputations were performed on 106 residents of Leverkusen (Germany) in 1990 and 1991. Of them, 82 (77.4%) had diabetes. Mean age was 72.0 years. In the case of multiple amputations, only the highest level was counted for the analysis. The following results were standardized to the German population. Incidence rates (100,000−1 · year−1) were determined to be as follows: for all amputations per total population, 33.8; for amputations in diabetic individuals per diabetic population, 209.2; for amputations in nondiabetic individuals per nondiabetic population, 9.4. Relative risk was 22.2; attributable risk among exposed, 0.96; population attributable risk, 0.72. When the study is repeated to monitor the St. Vincent targets (50% reduction), a reduction in the amputation rate in the diabetic population by 46% will be detected with 90% power.

CONCLUSIONS

We found incidence rates similar to those in the non-Indian population of the U.S. Great relative and population-attributable risks indicate that improving foot care in diabetic individuals appears to be the main target for the reduction of amputations in the general population.
The Effect of Metformin on the Metabolic Abnormalities Associated With Upper-Body Fat Distribution. BIGPRO Study Group
Authors: Fontbonne Annick , Charles M Aline , Juhan-Vague Irene , Bard Jean Marie , André Philippe , Isnard Françoise , Cohen Jean Marie , Grandmottet Pierre , Vague Philippe , Safar Michel E , Eschwège Eveline
Published: March 2007

OBJECTIVE

The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity.

RESEARCH DESIGN AND METHODS

Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups.

RESULTS

Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea.

CONCLUSIONS

The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.
A Comprehensive Assessment of the Avoidability of Long-Term Complications of Diabetes. A case-control study. SID-AMD Italian Study Group for the Implementation of the St. Vincent Declaration
Authors: Nicolucci Antonio , Cavaliere Donatella , Scorpiglione Nicola , Carinci Fabrizio , Capani Fabio , Tognoni Gianni , Benedetti Massimo Massi
Published: March 2007

OBJECTIVE

To identify and quantify risk factors for the development of long-term diabetic complications (i.e., critical limb ischemia, amputation, chronic renal failure [creatinine > 3 mg/dl], dialysis treatment, proliferative retinopathy, blindness), with particular emphasis on those variables that, being related to quality of care, can be considered avoidable.

RESEARCH DESIGN AND METHODS

We designed a case-control study that enrolled 886 patients with long-term diabetic complications and 1,888 control subjects without complications from 35 diabetic outpatient clinics and 49 general practitioners' offices during a 6-month period. Selected socioeconomic, pathophysiologic, self-care, health care, and lifestyle information were collected for all patients.

RESULTS

A logistic regression analysis showed that several factors are related to the development of major diabetic complications. Among patient characteristics, male sex (odds ratio [OR] = 1.8, 95% CI 1.4–2.3) and age (OR = 1.7, 95% CI 1.2–2.4 for patients between 50 and 69 years of age as opposed to those younger than 50 years of age) were associated with an increased risk of complication. Among clinical variables, the type and the duration of diabetes were the most important predictors of diabetic complications. The presence of hypertension was also associated with the development of diabetic complications, particularly when it was poorly controlled by treatment (OR = 3.1, 95% CI 2.3–4.3). Patients who needed help to reach a health care facility and those who did not regularly attend such a facility were at higher risk of developing complications (OR = 1.5, 95% CI 1.2–1.9; OR = 1.7, 95% CI 1.3–2.2, respectively). Educational aspects were also related to the outcome: patients who did not receive any kind of educational intervention had an increased risk of developing complications (OR = 4.1, 95% CI 1.7–9.7), while self-management of insulin therapy had a protective effect (OR = 0.6, 95% CI 0.5–0.8). The summary attributable risk related to avoidable risk factors (i.e., uncontrolled hypertension, poor compliance with visit scheduling, inadequate diabetes education, no self-management of insulin treatment) was 0.39.

CONCLUSIONS

Our data suggest that, by removing avoidable risk factors, the number of diabetic complications considered could be reduced by more than one-third. The case-control methodology represents an efficient way of monitoring clinical practice and relating it to important outcomes. It can be of help for policy makers in identifying the more effective strategies and in tailoring specific interventions aimed at improving the quality of the care delivered to diabetic patients.
Insulin Antibodies Do Not Preclude Optimization of Metabolic Control in Women With IDDM During Pregnancy
Authors: Dozio Nicoletta , Beretta Angelo , Castiglioni Mariatersa , Rosa Susanna , Scavini Marina , Belloni Cristina , Poloniato Antonella
Published: March 2007

OBJECTIVE

To evaluate whether the presence of insulin antibodies (IAs) may preclude the optimization of metabolic control during pregnancy and affect outcome in women with IDDM.

RESEARCH DESIGN AND METHODS

IAs were measured by radiobinding assay in 44 women with IDDM referred to the Diabetes and Pregnancy Outpatients' Clinic during 46 pregnancies. Age, duration of IDDM, metabolic control (HbA1c, mean pre- and postprandial capillary blood glucose, frequency of hypo- or hyperglycemia), insulin requirement at 1st and 3rd trimester of pregnancy, BM1, and weight gain were recorded. Neonatal variables such as gestational age, weight, length, and the presence at birth of either hypoglycemia, hypocalcemia, or jaundice requiring phototherapy were also considered.

RESULTS

IAs correlated positively with insulin requirement (P < 0.05) and negatively with HbA1c at term (P < 0.01). Patients with IA levels ≥ 40% insulin binding (8 of 46) had a higher insulin requirement and lower preprandial capillary blood glucose at the beginning of pregnancy but not at term (P < 0.005), whereas they had lower HbA1c at term than did patients with low IA levels (P < 0.01). IA levels decreased slightly at term (P = 0.007). IA levels ≥ 40% were not associated with a higher rate of hypo- or hyperglycemic episodes or with diabetic complications or thyreopathy. No correlation was found between LA levels and any of the neonatal variables considered.

CONCLUSIONS

The presence of IAs does not preclude optimization of metabolic control during pregnancy and is compatible with a favourable outcome.
Relationship of Glucose Tolerance and Plasma Insulin to the Incidence of Coronary Heart Disease: Results from Two Population Studies in Finland
Authors: Pyörälä Kalevi
Published: March 2007

The relationship of glucose tolerance to the incidence of coronary heart disease (CHD) has been investigated in two cohorts of Finnish men: 3267 men ages 40–59 yr from the Social Insurance Institution's (SII) Coronary Heart Disease Study and 1059 men ages 30–59 yr from the Helsinki Policemen Study. The relationship of plasma insulin level to the incidence of CHD was also investigated in the Helsinki Policemen Study. An oral glucose lead of 60, 75, or 90 g according to body surface area was used in both studies. In the SII Study, plasma glucose was determined from venous blood samples taken 1 h after glucose load. In the Helsinki Policemen Study, blood glucose was determined from venous blood samples taken at 0, 1, and 2 h, and at a 5-yr reexamination, plasma insulin was measured during OGTT at 0, 1, 2 h. In the SII Study cohort, the 4-yr mortality from CHD and the 4-yr incidence of nonfatal myocardial infarction (MI) did not show a definite relationship to 1-h postload plasma glucose. In the Helsinki Policemen Study cohort, the 5-yr incidence of “hard criteria” CHD (CHD death and nonfatal MI) was significantly related to high 1-h postload blood glucose level but not to fasting or 2-h postload blood glucose levels. 10-yr mortality from CHD was significantly higher in the top quintile of fasting and 1- and 2-h postload blood glucose levels, as was the incidence of “hard criteria” CHD. However, in multivariate analyses including age, systolic blood pressure, plasma cholesterol, and smoking, the blood glucose variables showed no statistically significant independent contribution in predicted risk of CHD. Univariate analyses by quintiles of plasma insulin levels measured at the 5-yr reexamination showed that the incidence of “hard criteria” CHD during the subsequent 5 yr was significantly higher in the top quintiles of fasting and 1-h and 2-h postload plasma insulin than in the combined lower quintiles. Multivariate analyses showed that the value of high 1-h or 2-h postload plasma insulin level for predicting CHD risk was independent of other risk factors, including blood glucose levels during OGTT.
Coronary Heart Disease Incidence and Cardiovascular Mortality in Busselton with Reference to Glucose and Insulin Concentrations
Authors: Welborn T A , Wearne K
Published: March 2007

In the 1966 study of the population of Busselton, Australia, blood sugar and serum insulin levels were measured one hour after an oral glucose load, in addition to the conventional cardiovascular risk factors. The six-year incidence of coronary heart disease (CHD) and the 12-yr mortality from CHD and from all cardiovascular diseases is described in relation to the initial baseline variables measured using the upper 20th percentile values (age-specific and sex-specific) to define the risk ratios. In younger subjects (ages less than 60 yr), elevated blood pressure levels for both sexes (risk ratios from 2.9 to 5.2) and elevated serum cholesterol concentrations for males (risk ratios from 3.0 to 3.3) were strong predictors of cardiovascular risk. In men aged 60 to 69 yr, those with upper range one-hour serum insulin concentrations showed marked associations with the six-year incidence of CHD, the 12-yr mortality from CHD, and the 12-yr mortality from all cardiovascular diseases (risk ratios were 2.0, 2.3, and 2.4, respectively). The relationship of elevated serum insulin and cardiovascular mortality persisted when males of all ages were analyzed, and it appeared to be independent of the other major risk factors. In females, no association between serum insulin and CHD or cardiovascular disease could be found. Although the age and sex specific upper 20th percentile values for one-hour blood sugar concentrations showed a low grade association in patients with subsequent cardiovascular disease end points, more noticeable risk ratios were demonstrated at the higher blood sugar level of 200 mg/100 ml or greater (in the age group 60 yr and over, risk ratios were 2.2 in males and 2.6 in females.
The WHO Multinational Study of Vascular Disease in Diabetes: 1. General Description
Authors: Jarrett R J , Keen H , Grabauskas V
Published: March 2007

A general description of the multinational study under the auspices of the World Health Organization is presented. The purpose was to compare the prevalence of vascular disease in representative samples of diabetic subjects of different ethnic and cultural habitus. Standardized methods of investigation were devised. Fourteen centers participated, and the data collected so far indicate that the characteristics of the populations studied varied as to age composition, adiposity, cigarette smoking, treatment, age at diagnosis, and duration of diabetes. Thus, taking these factors into consideration and while awaiting completion of the data, conclusions must be drawn with reserve.
Studies of the HLA System and Insulin-dependent Diabetes Mellitus
Authors: Christy Morten , Green Anders , Christau Bjorn , Kromann Hans , Nerup Jørn , Platz Per , Thomsen Mogens , Ryder Lars P , Svejgaard Arne
Published: March 2007

The relationship between the HLA system and insulin-dependent diabetes mellitus (IDDM) is reviewed. Data compiled by the HLA and Disease Registry reveal that HLA-B8 and/or Dw3 are associated with IDDM in all populations studied so far, but further population studies in non-Caucasian populations should be performed. In Caucasians, HLA-Dw2 renders protection against IDDM while HLA-Dw3 and Dw4 are associated with susceptibility to IDDM. The exact mode of inheritance of susceptibility to IDDM remains to be established. Involvement of at least two genes is likely. Heterogeneity of IDDM is highly possible and should be a matter of major interest in diabetes research.
Diabetes Mellitus: The Search for Genetic Markers
Authors: Rotter Jerome I , Rimoin David L
Published: March 2007

The search for genetic markers has established that idiopathic diabetes mellitus is a genetically heterogeneous group of disorders that have glucose intolerance in common. The types of genetic markers—subclinical linkage, and association—and how they are utilized to delineate the genetic basis of the diabetic syndrome are discussed. The use of such markers as insulin levels, pancreatic islet cell antibodies, and HLA antigens has permitted the separation of insulin-dependent (juvenile) and not insulin-dependent (maturity) diabetes. Such studies have also started to reveal heterogeneity within these broad groups of insulin-dependent and not insulin-dependent types. This extensive heterogeneity has major implications for understanding the pathogenesis and genetics of diabetic mellitus and is of potentially great clinical significance, since the natural history and complications may well differ between these different disorders.
Risk Factors Other Than Hyperglycemia in Diabetic Macrovascular Disease
Authors: Medalie Jack H
Published: March 2007

A five-year prospective follow-up study was done on 10,000 adult males in Israel. The end-points of diabetes mellitus—clinical and unrecognized myocardial infarction, angina pectoris, sudden death, and hypertension—were examined. The incidence rates rise with age and vary significantly by areas of birth, with the Middle Eastern and North African subjects having the highest incidence of diabetes but the lowest cardiovascular rates. A developmental medical model based on a historical-societal perspective is proposed to explain these findings. The major factors found on multivariate analysis in the development of diabetes mellitus are compared with those of the other cardiovascular end-points mentioned above. The similarities and differences between these risk factors are discussed, and I conclude that the prevention or alleviation of diabetic macrovascular disease needs a multifactorial approach against the major risk factors of the macrovascular complications as well as those related to diabetes, in the individual, family, and community.
Prevalence and Course of Diabetes Modified by Fasting Blood Glucose Levels: Implications for Diagnostic Criteria
Authors: O'Sullivan John B
Published: March 2007

Data from the epidemiologic survey in Sudbury, Massachusetts, demonstrate that the prevalence of new cases of diabetes, based on the USPHS criteria for the standard 3-h oral glucose tolerance test as originally published, was 0.7%. If a fasting blood sugar ≥ to 110 mg/dl had been required for those USPH diagnoses, the prevalence would have fallen to 0.28%. Further, if a peak serum insulin level of ≤ 60 μU/ml had been required, the original prevalence rate would have dropped to 0.02%. Data from a prospeh criteria for diabetes indicate by life table analyses that 41% show further deterioration of carbohydrate control over the first 13 yr of the study when the fasting blood sugar was < 110 mg/dl in the initial diagnostic test and 82% when the fasting blood sugar was ≥ to 110 mg/dl. The relationship of fasting blood glucose to later decompensation proved to be a continuous one without evidence of a threshold effect. The implications of both of these studies for diagnostic criteria, particularly recent proposals, is discussed.
Use of an artificial pancreas as a tool to determine subcutaneous insulin doses in juvenile diabetes
Authors: Lambert André E , Buysschaert Martin , Lambotte Luc
Published: March 2007

The present study was undertaken to examine the feasibility of determining the most appropriate subcutaneous insulin treatment in unstable diabetes on the basis of the circadian hormonal profile delivered by an artificial pancreas. The metabolic control of 11 brittle diabetic subjects, as assessed by the M value and the MAGE index (used as indexes of blood glucose control and of glycemic fluctuations, respectively), was compared during a 5-day period before and after a 24-h connection to the artificial pancreas. The usual insulin treatment was continued to that day. Examination of the insulin pattern revealed by the artificial pancreas suggested that a valid scheme for subsequent treatment should consist of two daily injections of a mixture of short-acting and intermediate-acting insulins, which was administered to the patients beginning with the injection given after the artificial pancreas onwards. The new insulin regimen was characterized by a total daily dose that increased from 0.93 ± 0.10 to 1.20 ± 0.10 U/kg body weight (mean ± SEM; P < 0.005) as well as by a higher proportion of the dose given as regular insulin (37.1 ± 6.9% before vs. 56.0 ± 2.1% after; P < 0.05). These changes led to a better control of blood glucose in 10 patients, as evidenced by a decrease of both the M value and the mean of all blood glucose levels. The mean MAGE index was not decreased, however, by the new insulin program, thereby suggesting that the lability of the disease remained unabated. These results indicate that subcutaneous treatment consisting of two daily injections of regular and intermediate-acting insulins and comprising 50 to 60% of the former could improve the metabolic control in unstable diabetes. The artifical pancreas provided a rapid and simple means to determine the appropriate doses for each type of insulin.
Glucosuria in Children with Diabetes: Advantages of the 2-Drop Clinitest Method
Authors: Winter Robert J , Traisman Howard S , Green Orville C
Published: March 2007

In order to assess the actual and theoretical limitations of using the traditional urinary glucose determinations as an indicator of plasma glucose concentration, we have measured plasma and urine glucose concentrations in 37 children with diabetes mellitus. A constant blood withdrawal system enabled an accurate estimate of the glucose concentration presented to the renal glomerulus over the 30-min period of blood collection and urine formation. The theoretical range of plasma glucose over which the 5-Drop and 2-Drop Clinitest methods are sensitive is 32 mg/dl and 81 mg/dl, respectively. This suggests that the 2-Drop method is the procedure of chioce for most insulin-dependent diabetic patients. Nevertheless, the extremely wide range of plasma glucose corresponding to a given urinary glucose measurement limits the precision with which any single urine test can be interpreted.
Hypoglycemia: Incidence and Clinical Predictors in a Large Population-Based Sample of Children and Adolescents with IDDM
Authors: Davis E A , Keating B , Byrne G C , Russell M , Jones T W
Published: March 2007

OBJECTIVE

To determine the frequency of moderate and severe hypoglycemia and to identify clinical predictors associated with its occurrence in a large population-based sample of children and adolescents with IDDM.

RESEARCH DESIGN AND METHODS

A total of 657 patients (age: 12.1 ± 4.4 years, mean ± SD) were included in the study, yielding 1,449 patient-years of data. A prospective assessment of severe hypoglycemia (an event resulting in a seizure or coma) and moderate hypoglycemia (an event requiring assistance of another, excluding severe episodes) was made over a 3-year period. Patients and caregivers detailed episodes of significant hypoglycemia (moderate and severe events) and these were recorded at each 3-month clinic visit along with HbA1c. Data were analyzed using generalized estimating equation models fitted with the exchange correlation structure.

RESULTS

The overall incidence of severe events was 4.8/100 patient-years and of moderate events was 13.1/100 patient-years. Over 3 years, severe events occurred in 8.5% of children and moderate events occurred in 26.9%. Significant hypoglycemia was rare in the first 12 months after diagnosis. Rates of hypoglycemia were increased in children < 6 years of age versus > 6 years of age (40.9 vs. 16.6/100 patient-years, age ≤6 years vs. age > 6 years, P < 0.001). Rates of hypoglycemia doubled when HbA1c fell below 8%, and children with HbA1c < 7% had a threefold increase in both moderate and severe hypoglycemia (e.g., severe episodes 14.9 vs. 4.1/100 patient-years, HbA1c ≤ 7% vs. HbA1c > 7%, P < 0.001). Most severe events were seizures, and 75% of them occurred at night. The majority of events were related to missed meals or increased activity. However, in 38% no predisposing factor was evident.

CONCLUSIONS

Newly diagnosed children appear to be protected from severe hypoglycemia. Rates increase with lower glycated hemoglobin, especially when mean HbA1c is < 8.0%. Younger children, who may be more susceptible to the adverse effects of neuroglycopenia, are at a particular risk of significant hypoglycemia.
Psychiatric Disorders in Youths With IDDM: Rates and Risk Factors
Authors: Kovacs Maria , Goldston David , Obrosky D Scott , Bonar Lisa K
Published: March 2007

OBJECTIVE

To determine prevalence rates, associated features and risk factors for psychiatric disorders subsequent to the diagnosis of IDDM in youths.

RESEARCH DESIGN AND METHODS

Using a longitudinal, naturalistic design, 92 youths from 8 to 13 years old at onset of IDDM were followed from their initial diagnosis. They were repeatedly assessed by semistructured interview and diagnosed by operational criteria.

RESULTS

By the 10th year of IDDM and the mean age of 20 years, an estimated 47.6% of the sample developed psychiatric disorder. Major depressive, conduct, and generalized anxiety disorders were the most prevalent, and major depression had a significantly higher estimated rate (27.5%) than each other disorder. The highest incidence rates were during the 1st year of the medical condition. Initial maternal psychopathology increased the risk of psychiatric disorder in the subjects, and maternal depression was a specific risk factor for depression in the subjects. Earlier psychiatric disorder in the subjects also increased the risk of later disorder.

CONCLUSIONS

The results converge with findings from other studies, suggesting elevated psychiatric morbidity in contemporary samples of young people with IDDM. The morbidity partly reflects the high incidence of major depression in adolescence and generalized anxiety disorder in young adulthood. Monitoring the psychological status of young patients and their mothers may help to identify diabetic children at risk for psychiatric disorder and facilitate prevention or treatment efforts. Monitoring may be particularly beneficial during the 1st year of the IDDM.
Major Depressive Disorder in Youths With IDDM: A controlled prospective study of course and outcome
Authors: Kovacs Maria , Obrosky D Scott , Goldston David , Drash Allan
Published: March 2007

OBJECTIVE

To determine whether IDDM affects the course of major depressive disorder (MDD) in youths.

RESEARCH DESIGN AND METHODS

The study samples include 24 youths with IDDM (of a group of 92) who developed MDD during a longitudinal follow-up of 10 years, on average, since onset of the medical condition, and 30 depressed psychiatric control subjects, matched on relevant variables. Both groups were repeatedly assessed by semistructured interviews and diagnosed by operational criteria.

RESULTS

In diabetic subjects, median time to recovery from the first episode of MDD was 6.4 months; by 12 months from onset, 69% of the youths will have recovered. Within 2 years of recovery, 32% were at risk for a new episode; by 6.5 years, altogether 47% are estimated to have a recurrence. Only 37.5% of diabetic subjects received treatment for the first episode of depression, and 50% received treatment for the second episode. Overall rates of recovery and recurrence were indistinguishable in the diabetic and psychiatric control groups. However, young women with diabetes were at nine times greater risk for recurrent depression than their male counterparts, and diabetic subjects eventually spent more time being depressed than the control subjects.

CONCLUSIONS

The course characteristics of MDD in young diabetic subjects and psychiatric control subjects appear to be similar in several regards. However, the eventual propensity of diabetic youths for more protracted depressions and the higher risk of recurrence among young diabetic women suggest that the mental health of patients with IDDM should be closely monitored. The findings confirm that depression is undertreated among patients in the primary health care sector.
The Effect of Prepubertal Diabetes Duration on Diabetes: Microvascular Complications in Early and Late Adolescence
Authors: Donaghue Kim C , Fung Amelia TW , Hing Stephen , Fairchild Jan , King Jennifer , Chan Albert , Howard Neville J , Silink Martin
Published: March 2007

OBJECTIVE

To define the significance of prepubertal diabetes duration in the development of diabetic microvascular complications in adolescents.

RESEARCH DESIGN AND METHODS

Study A compares complications in 38 prepubertal (PreP) and 140 pubertal (Pub) subjects of the same age (10-14 years) and diabetes duration (3–12 years) to determine if the absence of puberty itself confers a lower risk of complications. Study B examines the importance of prepubertal and pubertal diabetes duration in 193 older adolescents (ages 15–22 years) with prepubertal onset of diabetes. Retinopathy status was assessed using stereoscopic fundus photography of seven fields per eye. Albumin excretion rate (AER) was assessed by three consecutive overnight urine collections, using a polyclonal radioimmunoassay.

RESULTS

In study A, there were no significant differences between the PreP and Pub groups for retinopathy (27 vs. 29%, P = 0.8) or differences in elevated AER (17 vs. 31%, P = 0.1). In study B, longer prepubertal diabetes duration improved the prediction for retinopathy over postpubertal duration alone (P < 0.0005). No relationship with duration was found for elevated AER (> 7.5, > 15, and > 30 micrograms/min).

CONCLUSIONS

Prepubertal subjects with diabetes did not have less retinopathy or elevated albumin excretion compared with pubertal subjects of the same age. Prepubertal diabetes duration is significantly related to the presence of retinopathy in adolescents.
Increased Urinary Albumin and Retinol-Binding Protein in Type I Diabetes: A study of identical twins
Authors: Dubrey Simon W , Beetham Robert , Miles Judith , Noble Mark IM , Rowe Rachel , Leslie R David G
Published: March 2007

OBJECTIVE

Indexes of early renal glomerular and tubular dysfunction have been demonstrated in type I diabetes, but it remains uncertain whether such changes are genetically determined or are secondary to the disease process. We therefore undertook to study whether early markers of renal dysfunction are a consequence of type I diabetes or inherited.

RESEARCH DESIGN AND METHODS

We estimated both urinary albumin excretion (UAE) and urinary retinol-binding protein (RBP) in 51 identical twin pairs discordant for type I diabetes and in 51 matched control subjects.

RESULTS

UAE and RBP were significantly higher in the diabetic twins than in their nondiabetic co-twins (P < 0.0001 and P < 0.0002, respectively). Seven diabetic twins had elevated UAE, but none of the nondiabetic co-twins did. In a subgroup of 44 twins with normal UAE (albumin excretion rate < 20 micrograms/min), diabetic twins had both a higher albumin excretion function (median [range]; 0.64 [0.18–2.74] mg/mmol creatinine) than their nondiabetic co-twins (0.48 [0.24–1.40], P < 0.01) and higher levels of RBP excretion (10.4 [4.0–167.0] micrograms/mmol creatinine) than their nondiabetic co-twins (7.5 [0.97–23.0], P < 0.05). Values between twins of a pair were significantly correlated for RBP (r = 0.36, P < 0.05) but not for UAE (r = 0.13).

CONCLUSIONS

These results suggest that in type I diabetes, an index of renal tubular function (RBP), but not glomerular function (UAE), is influenced by shared genetic and nongenetic factors. Type I diabetes can affect renal tubular function even when glomerular function is normal. We conclude that neither the increased UAE nor urinary RBP found in type I diabetes is inherited independently of the diabetes process.
Impact of Dosage Frequency on Patient Compliance
Authors: Paes Arsenio H P , Bakker Albert , Soe-Agnie Carmen J
Published: March 2007

OBJECTIVE

To evaluate the impact of dosage frequency on the compliance of patients who receive their medicines from community pharmacies.

RESEARCH DESIGN AND METHODS

Each month, patients received a supply of their medication in a Medication Event Monitoring Systems container, which registered each opening of the package. At the end of the study, the patients received a short questionnaire. The subjects were 91 diabetic patients using oral antidiabetic agents. Patients taking insulin and those who were unable to collect their medicines from the pharmacy were excluded from the study. Compliance was defined as the percentage of doses taken during the observation period. Another parameter used was compliance with the prescribed regimen, defined as the percentage of days in which the number of tablets were taken as prescribed. As a last parameter, compliance with the prescribed dose intervals was used.

RESULTS

Compliance is influenced by the frequency of doses. The compliance for this group of patients is 74.8%, with an average of 79% in the case of a dose once daily and 38% in the case of a dose three times daily. The predominant type of noncompliance in all groups was dose omissions. However, more than one-third of the patients used more doses than prescribed. Overconsumption is a frequently made mistake by patients on a one-dose daily schedule.

CONCLUSIONS

The reduction of dose frequency may decrease total noncompliance, but at the same time, it increases the risk of overconsumption. Reducing the frequency does not automatically result in a better therapeutic schedule. The choice of once or twice daily should depend on the therapeutic range of the drug.
Relationship Between Gastric Emptying and an α-Glucosidase Inhibitor Effect on Postprandial Hyperglycemia in NIDDM Patients
Authors: Kawagishi Takahiko , Nishizawa Yoshiki , Taniwaki Hiromichi , Tanaka Shinji , Okuno Yasuhisa , Inaba Masaaki , Ishimura Eiji , Emoto Masanori , Morii Hirotoshi
Published: March 2007

OBJECTIVE

The purpose of the study was to examine the relationship between gastric emptying and the efficacy of an α-glucosidase inhibitor in NIDDM patients.

RESEARCH DESIGN AND METHODS

Sixteen NIDDM patients (4 patients treated with diet therapy alone and 12 receiving a sulfonylurea) were given 0.6 mg of voglibose daily for 4 weeks. The efficacy of voglibose was assessed by measurement of HbA1c, fasting plasma glucose, and 45- and 120-min postprandial plasma glucose (PPG) and serum insulin concentrations before and after the 4 weeks of voglibose therapy. Gastric emptying was evaluated using the proportional cumulative area under the absorption curve (% AUC) of plasma acetaminophen concentration at 60 min after ingestion of a liquid test meal containing 20 mg/kg of acetaminophen. These measurements were also taken before and after the therapy.

RESULTS

The change in the 45-min PPG levels from the fasting state correlated significantly with the % AUC of the plasma acetaminophen concentrations (r = 0.625, P = 0.0096) before the voglibose administrations. The mean 45-min and 2-h PPG levels were reduced significantly after 4 weeks of voglibose (P < 0.05 and P < 0.01, respectively). Two-hour postprandial serum insulin concentrations were also significantly reduced at the end of the treatment period (P < 0.05). The changes in the PPG levels between pre- and posttreatment periods correlated significantly with the % AUC of the plasma acetaminophen concentrations before the treatment period (r = 0.499, P = 0.0490; r = 0.713, P = 0.0019, respectively). There was no significant difference in the plasma acetaminophen concentrations between pre- and posttreatment periods.

CONCLUSIONS

The rate of gastric emptying affects the efficacy of voglibose therapy in NIDDM patients. Voglibose did not however alter the rate of gastric emptying.
Modification of Postprandial Hyperglycemia With Insulin Lispro Improves Glucose Control in Patients With Type 2 Diabetes
Authors: Feinglos Mary N , Thacker Connie H , English Jennifer , Bethel M Angelyn , Lane James D
Published: March 2007

OBJECTIVE

Insulin lispro is a rapid-acting analog of human insulin that can be used to target the postprandial rise in plasma glucose. We designed an open-label randomized crossover study of type 2 diabetic patients with secondary failure of sulfonylurea therapy to determine whether improvement of postprandial hyperglycemia would affect total daily glucose control.

RESEARCH DESIGN AND METHODS

Twenty-five type 2 diabetic patients who were poorly controlled on a maximum dose of sulfonylureas were studied in a university hospital clinical research center. In one arm of the study, patients continued therapy with maximum-dose sulfonylureas. In the other arm, patients used a combination therapy with insulin lispro before meals and sulfonylureas. After 4 months, patients were crossed over to the opposite arm. Fasting plasma glucose (FPG) and 1- and 2-h postprandial glucose (after a standardized meal), HbA1c, total, HDL, and LDL cholesterol, and triglyceride levels were measured at the end of each arm of the study.

RESULTS

Insulin lispro in combination with sulfonylurea therapy significantly reduced 2-h postprandial glucose concentrations compared with sulfonylureas alone, from 18.6 to 14.2 mmol/l (P < 0.0001), and incremental postprandial glucose area from 617.8 to 472.9 mmol · min · 1−1 (P < 0.0007). FPG levels were decreased from 10.9 to 8.5 mmol/l (P < 0.0001), and HbA1c values were reduced form 9.0 to 7.1% (P < 0.0001). Total cholesterol was significantly decreased in the lispro arm from 5.44 to 5.10 mmol/l (P < 0.02). HDL cholesterol concentrations were increased in the lispro arm from 0.88 to 0.96 mmol/l (P < 0.01). The patients weighed significantly more after lispro therapy than after sulfonylureas alone, but the difference was small in absolute terms (sulfonylurea therapy alone, 90.6 kg; lispro therapy, 93.8 kg; P < 0.0001). Two episodes of hypoglycemia (glucose concentrations, < 2.8 mmol/l) were reported by the patients while using lispro.

CONCLUSIONS

Previously, it has not been possible to address the effect of treatment of postprandial hyperglycemia specifically. We have now shown that the treatment of postprandial hyperglycemia with insulin lispro markedly improves overall glucose control and some lipid parameters in patients with type 2 diabetes.