bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Raloxifene on Serum Triglycerides in Women With a History of Hypertriglyceridemia While on Oral Estrogen Therapy
Authors: Carr Molly C. , Knopp Robert H. , Brunzell John D. , Wheeler Barbara S. , Zhu Xiaodong , Lakshmanan Mark , Rosen Amy S. , Anderson Pamela W.
Published: March 2007

OBJECTIVE—Raloxifene hydrochloride is a selective estrogen receptor modulator that to date has not been shown to cause hypertriglyceridemia in normal, diabetic, or hypertriglyceridemic women. This study was designed to assess the effect of raloxifene on serum triglycerides in postmenopausal women who have a history of increased hypertriglyceridemia with oral estrogen therapy.

RESEARCH DESIGN AND METHODS—This was a single-center, uncontrolled, open-label study investigating the effects of 8 weeks of raloxifene (60 mg/day) therapy on plasma lipids. The study subjects were 12 postmenopausal women, ages 49–73 years, with a documented history of oral estrogen–induced hypertriglyceridemia (serum triglycerides ≥3.39 mmol/l [≥300 mg/dl]).

RESULTS—At week 2 of the study, three (25%) of the subjects withdrew from the trial because they developed marked hypertriglyceridemia (≥11.3 mmol/l [≥1,000 mg/dl]) during raloxifene therapy. These three women had higher baseline triglyceride and glucose levels, were not being treated with lipid-lowering agents, and were more likely to have diabetes than the other study subjects. The remaining nine patients (75%) completed the 8-week trial and experienced a nonsignificant increase in mean triglyceride levels from baseline to end point. Raloxifene treatment also resulted in a significant 16% decrease in hepatic lipase activity and a 26% increase in HDL2 levels (P = 0.013 and 0.03, respectively).

CONCLUSIONS—Patients with a previous history of hypertriglyceridemia on oral estrogen therapy should have serum triglyceride levels monitored closely after beginning raloxifene therapy and may even require fibrate therapy before beginning raloxifene.
Insulin-Sensitizing Antihyperglycemic Drugs and Mortality After Acute Myocardial Infarction
Authors: Inzucchi Silvio E. , Masoudi Frederick A. , Wang Yongfei , Kosiborod Mikhail , Foody Joanne M. , Setaro John F. , Havranek Edward P. , Krumholz Harlan M.
Published: March 2007

OBJECTIVE—Thiazolidinediones (TZDs) and metformin are insulin-sensitizing antihyperglycemic agents with reported benefits on atherosclerosis. Despite extensive use in patients with diabetes and cardiovascular disease, there is a paucity of outcomes data with metformin and none yet with TZDs. We sought to determine the impact of these insulin sensitizers on outcomes in diabetic patients after hospitalization with acute myocardial infarction (AMI).

RESEARCH DESIGN AND METHODS—We conducted a retrospective cohort study of 24,953 Medicare beneficiaries with diabetes discharged after hospitalization with AMI between April 1998 and March 1999 or July 2000 and June 2001. The independent association between discharge prescription for metformin, TZD, or both agents and outcomes at 1 year was assessed in multivariable Cox proportional hazards models, adjusting for patient, physician, and hospital variables. The primary outcome was time to death within 1 year of discharge; secondary outcomes were time to first rehospitalization within 1 year of discharge for AMI, heart failure, and all causes.

RESULTS—There were 8,872 patients discharged on an antihyperglycemic agent, of which 819 were prescribed a TZD, 1,273 metformin, and 139 both drugs. After multivariable analysis, compared with patients prescribed an antihyperglycemic regimen that included no insulin sensitizer, mortality rates were not significantly different in patients treated with either metformin (hazard ratio [HR] 0.92 [95% CI 0.81–1.06]) or a TZD (0.92 [0.80–1.05]) but were lower in those prescribed both drugs (0.52 [0.34–0.82]). The results were similar among patients with heart failure. The prescription of a TZD was associated with a borderline higher risk of all-cause readmission (1.09[1.00–1.20]), predominately due to a higher risk for heart failure readmission (1.17 [1.05–1.30]).

CONCLUSIONS—Individually, prescription of insulin-sensitizing drugs is not associated with a significantly different risk of death in older diabetic patients within 1 year following AMI compared with other antihyperglycemic agents. Combined, however, metformin and TZDs may exert benefit. TZD prescription is associated with a higher risk of readmission for heart failure after myocardial infarction.
Urinary Incontinence and Diabetes in Postmenopausal Women
Authors: Jackson Sara L. , Scholes Delia , Boyko Edward J. , Abraham Linn , Fihn Stephan D.
Published: March 2007

OBJECTIVE—This study evaluates diabetes characteristics and other risk factors for urinary incontinence among community-dwelling postmenopausal women.

RESEARCH DESIGN AND METHODS—We performed a cross-sectional analysis of a population-based study of 1,017 postmenopausal women (218 with diabetes), aged 55–75 years, enrolled from a health maintenance organization. Outcomes included any incontinence and severe incontinence in the prior month.

RESULTS—Overall, 60% of women had any incontinence in the prior month and 8% had severe incontinence. Parity and postvoid residual bladder volume were not associated with incontinence. Oral estrogen and vaginal estrogen use were positively associated with a report of any incontinence but not severe incontinence. A history of urinary tract infection (UTI) and measures of general health were associated with both outcomes. Women with diabetes reported disproportionately more severe incontinence, difficulty controlling urination, mixed (stress and urge) incontinence, use of pads, inability to completely empty the bladder, being unaware of leakage, and discomfort with urination (P ≤ 0.06). Diabetes duration, treatment type, peripheral neuropathy, and retinopathy were significantly associated with severe incontinence in multiple regression models adjusted for age, education, and history of UTI (P = 0.01–0.06); however, additional adjustment for BMI diminished the strength of association (P = 0.17–0.52).

CONCLUSIONS—Urinary incontinence is highly prevalent among postmenopausal women. Women with diabetes are more likely to experience severe and symptomatic urinary incontinence. UTI history is a major risk factor, postvoid residual bladder volume plays no demonstrable role, and BMI confounds the relationship between diabetes and incontinence among healthy postmenopausal women.
Liver Enzymes, the Metabolic Syndrome, and Incident Diabetes
Authors: Nannipieri Monica , Gonzales Clicerio , Baldi Simona , Posadas Rosalinda , Williams Ken , Haffner Steven M. , Stern Michael P. , Ferrannini Ele
Published: March 2007

OBJECTIVE—To test the hypothesis that enzymes conventionally associated with liver dysfunction (aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase [GGT], and alkaline phosphatase) may predict diabetes.

RESEARCH DESIGN AND METHODS—From a population-based diabetes survey, we selected 1,441 men and women in whom serum enzyme levels were ≤3 SDs of the mean population value, alcohol intake was <250 g/week, and hepatitis B and C virus testing was negative. At follow-up (7 years), 94 subjects developed diabetes and 93 impaired glucose tolerance (IGT).

RESULTS—At baseline, all four enzymes were related to most of the features of the metabolic syndrome. After controlling for sex, age, adiposity/fat distribution, alcohol intake, serum lipids, and blood pressure, higher alanine aminotransferase and GGT values were significantly (P < 0.01) associated with both IGT and diabetes, whereas alkaline phosphatase was associated with diabetes only (P = 0.0004) and aspartate aminotransferase with IGT only (P = 0.0001). Raised GGT alone was associated with all the features of the metabolic syndrome. Raised GGT was a significant predictor of either IGT or diabetes (odds ratio 1.62 [95% CI 1.08–2.42] top quartile vs. lower quartiles, P < 0.02) after controlling for sex, age, adiposity/fat distribution, alcohol consumption, fasting plasma insulin and proinsulin levels, and 2-h postglucose plasma glucose concentrations.

CONCLUSIONS—Although mild elevations in liver enzymes are associated with features of the metabolic syndrome, only raised GGT is an independent predictor of deterioration of glucose tolerance to IGT or diabetes. As GGT signals oxidative stress, the association with diabetes may reflect both hepatic steatosis and enhanced oxidative stress.
Improved Meal-Related β-Cell Function and Insulin Sensitivity by the Dipeptidyl Peptidase-IV Inhibitor Vildagliptin in Metformin-Treated Patients With Type 2 Diabetes Over 1Year
Authors: Ahrén Bo , Pacini Giovanni , Foley James E. , Schweizer Anja
Published: March 2007

OBJECTIVE—To examine the effects of dipeptidyl peptidase-IV (DPP-4) inhibition on meal-related β-cell function and insulin sensitivity over 52 weeks in type 2 diabetes.

RESEARCH DESIGN AND METHODS—In a 12-week core study, placebo (n = 51) or vildagliptin (n = 56; 50 mg OD) was added to metformin treatment (1.5–3.0 mg/day). A 40-week extension followed in 71 patients. Meal tests were performed at 0, 12, 24, and 52 weeks; glucose, insulin, and C-peptide were evaluated.

RESULTS—In subjects completing 52 weeks with participation in all meal tests (n = 57), HbA1c (A1C) decreased in the vildagliptin/metformin group (VM group, n = 31) but increased in the placebo/metformin group (PM group, n = 26; between-group difference −1.0 ± 0.2%; P < 0.001; baseline of all subjects combined 7.7 ± 0.1%). Also, fasting glucose decreased in the VM group but increased in the PM group (difference −0.9 ± 0.3 mmol/l, P = 0.016; baseline 9.8 ± 0.3 mmol/l). Insulin secretion (postmeal suprabasal area under the 0- to 30-min C-peptide curve divided by the 30-min increase in glucose) was increased in the VM group but was reduced in the PM group (difference +0.011 ± 0.03 pmol/l 30 min/mmol/l, P = 0.018; baseline 0.036 ± 0.02). Insulin sensitivity during meal ingestion (oral glucose insulin sensitivity) increased in the VM group but was not altered in the PM group (difference +27 ± 4 ml · min−1 · m−2, P = 0.036; baseline 246 ± 6). Insulin secretion related to insulin sensitivity (adaptation index) increased in the VM group but decreased in the PM group (difference +3.2 ± 1.0, P = 0.040; baseline 9.1 ± 0.5). The change in adaptation index correlated to the change in A1C (r = −0.39, P = 0.004).

CONCLUSIONS—This study presents evidence that DPP-4 inhibition by vildagliptin when added to metformin in type 2 diabetes over 52 weeks improves β-cell function along with improved postmeal insulin sensitivity.
Effect of Low-Dose Insulin Treatment on Body Weight and Physical Development in Children and Adolescents at Risk for Type 1 Diabetes
Authors: Rhodes Erinn T. , Wolfsdorf Joseph I. , Cuthbertson David D. , Feldman Henry A. , Ludwig David S. ,   the DPT-1 Study Group
Published: March 2007

OBJECTIVE—Insulin’s role in body weight regulation is controversial. We evaluated the effect of parenteral insulin on body weight and physical development in children and adolescents at risk for type 1 diabetes.

RESEARCH DESIGN AND METHODS—We performed a secondary analysis of the parenteral arm of the Diabetes Prevention Trial–Type 1 Diabetes (DPT-1), a randomized controlled trial of low-dose parenteral insulin (human ultralente insulin at 0.25 units · kg−1 · day−1) in subjects with a >50% 5-year risk of diabetes. Analysis was limited to 100 subjects (55 intervention, 45 closely monitored) aged <19 years at randomization whose weight was followed for at least 2 years by study end after excluding subjects who were noncompliant within 2 years or developed diabetes within 36 months of randomization.

RESULTS—Subjects ranged in age from 4.07 to 18.98 years. There were no significant differences at randomization between subjects in each group with respect to sex, age, weight, height, BMI, Tanner stage, or glucose tolerance. We found no differences over 2 years between the intervention and closely monitored groups in the change in weight (median 6.8 vs. 6.0 kg, P = 0.65), height (median 10.7 vs. 10.1 cm, P = 0.66), BMI (median 0.9 vs. 1.0 kg/m2, P = 0.79), or Tanner stage (median 0 vs. 0, P = 0.35). Multiple regression showed no effect of insulin on change in weight (P = 0.53) or BMI (P = 0.95) over 2 years after adjustment for relevant covariates.

CONCLUSIONS—Low-dose insulin treatment for 2 years did not affect the weight, BMI, or physical development of nondiabetic children and adolescents.
Oral Contraceptives, Angiotensin-Dependent Renal Vasoconstriction, and Risk of Diabetic Nephropathy
Authors: Ahmed Sofia B. , Hovind Peter , Parving Hans-Henrik , Rossing Peter , Price Deborah A. , Laffel Lori M. , Lansang M. Cecilia , Stevanovic Radomir , Fisher Naomi D.L. , Hollenberg Norman K.
Published: March 2007

OBJECTIVE—Diabetes, the leading cause of end-stage renal disease in the U.S., is believed to involve activation of the renin angiotensin system (RAS) as a risk factor for nephropathy. RAS activation occurs in healthy women using oral contraceptives (OCs), but the effects of OC use on the diabetic kidney are unclear.

RESEARCH DESIGN AND METHODS—Renal plasma flow (RPF) response to captopril, as an index of RAS activity, was investigated in 92 women (41 nondiabetic OC nonusers, 10 nondiabetic OC users, 29 diabetic OC nonusers, and 12 diabetic OC users). Based on the hemodynamic findings, we examined the impact of OC use on the development of nephropathy as a post hoc analysis in an inception cohort of 114 female patients with newly diagnosed type 1 diabetes followed for a median of 20.7 years (range 1–24).

RESULTS—Nondiabetic OC nonusers showed minimal RPF vasodilator response to captopril (9 ± 10 ml · min−1 · 1.73 m−2, P = 0.6). In comparison, nondiabetic OC users showed a significant increase (69 ± 35 ml · min−1 · 1.73 m−2, P = 0.02) (P = 0.04 vs. nondiabetic OC nonusers). Diabetic OC nonusers demonstrated the anticipated vasodilator response (58 ± 12 ml · min−1 · 1.73 m−2, P < 0.0001). Diabetic OC users showed the largest responses (84 ± 12 ml · min−1 · 1.73 m−2, P = 0.002) (P = 0.04 vs. diabetic OC nonusers). Plasma renin activity did not vary with OC use (P = 0.3). The RPF responses to captopril and angiotensin receptor blocker were highly correlated (r = 0.72, P < 0.001), suggesting clear involvement of the RAS. In the observational study, 18% (6/33 [95% CI 4.3–32.1]) of OC users developed macroalbuminuria compared with 2% (2/81 [0–5.9]) of OC nonusers (P = 0.003, univariate analysis). After adjustment for known risk factors with a Cox regression model, OC use remained a predictor for the development of macroalbuminuria (relative risk 8.90 [95%CI 1.79–44.36], P = 0.008).

CONCLUSIONS—The strong association of OC use with angiotensin-dependent control of the renal circulation and the development of macroalbuminuria suggest that OC use may be a risk factor for diabetic nephropathy. Large prospective studies are required to further investigate this relationship.
The Effect of Transition from Traditional to Urban Life-Style on the Insulin Secretory Response in Australian Aborigines
Authors: O'Dea Kerin , Spargo Randolf M , Akerman Kim
Published: March 2007

Recent epidemiologic studies have revealed a high prevalence of maturity-onset diabetes in certain populations that have undergone comparatively rapid urbanization. There is evidence suggesting that Australian Aborigines may respond to urbanization in this way. Thirteen full-blood Aborigines from the Mowanjum Community, Derby, Western Australia, cooperated in the present study. They spent 3 mo living in their traditional hunter-gatherer life-style, after which their insulin response to glucose was measured in a starch tolerance test. The findings were compared in follow-up studies conducted 3 mo after returning to their urban environment. Similar studies were conducted in Caucasians of comparable age and weight. Fasting glucose concentrations were lower in Aborigines than in Caucasians and were unaffected by life-style changes. Although basal insulin levels were similar in the three groups, there were striking intergroup differences in the insulin responses to glucose. The areas under the insulin curves in the first hour after starch ingestion were: urban Aborigines 4478 ± 465 μU/ml−1/min, traditional Aborigines 2959 ± 301 μU/ml−1/min, and Caucasians 2097 ± 224 μU/ml−1/min. This appeared to reflect differences in the early rates of change of glucose concentrations. The data suggest that these Aborigines have an abnormally high insulin response to glucose, which is ameliorated, but not normalized, by reverting to their traditional life-style.
Noneffect of Isoniazid on Urine Glucose Tests
Authors: Self Timothy H , Wester Vicki L
Published: March 2007

Isoniazid has been shown by in vitro study to reduce Clinitest tablets. The effect of isoniazid on urine glucose tests was investigated in 30 patients by comparing commonly used glucose oxidase methods to Clinitest. Study results indicate that isoniazid does not cause clinically significant interference with the copper reduction method for urine glucose determination.
Glucose Tolerance and Blood Lipids in Bran-Fed Patients with Impaired Glucose Tolerance
Authors: Bosello Ottavio , Ostuzzi Roberto , Armellini Fabio , Micciolo Rocco , Scuro Ludovico A
Published: March 2007

Thirty-eight patients (13 men and 25 women) with impaired glucose tolerance, aged 33–70 yr, underwent a dietary program adding 20 g of raw bran to their usual diet without changing their dietary habits. After 1 mo of treatment, the areas under the curves for glucose and insulin were reduced from 26,214 ± 5618 to 24,529 ± 5207 g/min (P < 0.001) and from 15,893 ± 9714 to 12,440 ± 7377 mU/min (P < 0.001), respectively, cholesterol was reduced from 234 ± 40 to 212 ± 29 mg/dl (P < 0.001), and triglycerides were reduced from 108 ± 56 to 97 ± 50 mg/dl (P < 0.05). Body weight (initially 128.44% relative body weight) decrease 0.8% (P < 0.02). After the first month, 14 subjects were studied for a further 2 mo. Six patients continued bran feeding, and eight, who stopped bran, were used as controls. Patients who took bran maintained metabolic improvement over the 3-mo treatment period, while those who stopped bran did not.
Pectin: An Examination in Normal Subjects
Authors: Gold Larry A , McCourt Jerome P , Merimee Thomas J
Published: March 2007

Pectin (10 g) administered to normal subjects with 100 g of glucose did not alter significantly serum concentrations of either glucose or insulin compared with glucose given alone. Pectin given with a mixed meal, however, did reduce the degree of glycemia without significantly altering insulin secretion. Pectin given with meals for 18 days was without effect on either serum glucose or insulin concentrations.
Efficacy of Low-Dose Insulin Therapy for Severely Obtunded Patients in Diabetic Ketoacidosis
Authors: Morris Lawrence R , Kitabchi Abbas E
Published: March 2007

To evaluate the efficacy of low-dose insulin therapy in cases of severe diabetic ketoacidosis (DKA), we examined admission clinical and biochemical parameters and responses to therapy in 48 diabetic patients who presented with DKA and were randomized to receive either high- or low-dose insulin. There were no differences in the initial clinical and biochemical parameters of the patients, regardless of assignment to low or high dose; however, a subgroup of 13 patients who were classified as severe DKA (based on their presentation in a comatose or stuporous state) had, as expected, more marked clinical and biochemical abnormalities than their alert cohorts. The responses to therapy (rate of glucose decrement and control of acidosis) were comparable in the high-dose and low-dose groups of comatose/stuporous patients and were not significantly different from the noncomatose cohorts. These data indicate that low-dose insulin therapy in severely ill comatose patients is as effective as high-dose.
Blood Glucose Control During Pregnancy
Authors: Skyler Jay S , O'Sullivan Mary Jo , Robertson Euan G , Skyler Denise L , Holsinger Kathleen K , Lasky Ilene A , McLeod Allen G W , Burkett Gene , Mintz Daniel H
Published: March 2007

Pregnant diabetic women represent a unique category of patient in whom diabetic control is most desirable, since even minor degrees of hyperglycemia have adverse effects on the conceptus. In 18 insulin-dependent pregnant diabetic women (White Class B, N = 4; C, N = 5; D, N = 7; and R, N =2), we have utilized a therapeutic program consisting of intensive patient education, a multiple-component insulin regimen (two to four injections daily), careful dietary control, and meticulous balancing of food, activity, and insulin dosage, monitoring such balance with patient-determined blood glucose measurements four to seven times daily using the Dextrostix/Eyetone system. Our goals for blood glucose management have been to attain fasting levels of 60–90 mg/dl, preprandial levels less than 105 mg/dl, and postprandial levels less than 120 mg/dl, in the absence of significant hypoglycemia. We have been able to attain these goals for most of the period of monitoring in the majority of these patients, while in the others we have achieved marked improvement in diabetic control, although we did not consistently attain our goals. Despite this, there was not infrequent neonatal morbidity, including a 33% frequency of macrosomia, an 11% frequency of significant hypoglycemia, and a 22% frequency of congenital malformation. Nevertheless, all infants survived and are generally healthy, whereas only 38% of 21 previous pregnancies in these same women have eventuated in living offspring. Thus, although further refinement is clearly indicated, it appears that our approach has resulted in improved pregnancy outcome. Patient self-monitoring of blood glucose is a procedure that is relatively simple, practical, acceptable to patients, and facilitates the attainment of glycemic control.
The Significance of the Cerebrospinal Fluid Examination in the Management of Chlorpropamide-induced Hypoglycemia
Authors: Kaplinsky Naomi , Frankl Otto
Published: March 2007

Chlorpropamide-induced hypoglycemia is often overlooked, misdiagnosed, and mistreated, because of the atypical, insidious, and intermittent clinical picture and because of the normal serum glucose level in some of the patients when arriving at the hospital. These facts are demonstrated in three case reports. Since the correction of low glucose levels in the cerebrospinal fluid occurs hours after its correction in the serum, examining and at times following the cerebrospinal fluid glucose levels in patients with chlorpropamide-induced neuroglycopenia will enable physicians to diagnose and cure more patients. A high index of suspicion should exist in the presence of any atypical encephalopathy, mainly in the elderly diabetic patient treated with chlorpropamide and suffering from impaired cerebral, hepatic, or renal function. By suspecting and identifying neuroglycopenia, disabling residual deficits and even death could eventually be prevented.
Insulin Kinetics, Models, and Delivery Schedules
Authors: Berman Mones
Published: March 2007

Several insulin models are examined as to their responses to various insulin inputs and glucose utilization and production control. It is shown that the action of insulin on glucose utilization correlates best with model compartments having a 30–50-min delay compared with plasma, whereas glucose production control is rapid. It is further shown that whereas the predicted plasma insulin response curves are nearly the same for various models, the responses at possible sites of action (e.g., receptors or slowly exchanging tissues) can differ considerably for the different models. By determining the parameter values for the glucose-insulin system in a patient through isotope kinetics studies, it is possible to use the patient's model either as a direct algorithm for insulin delivery or as a tool for studying glucose control under various conditions and thus aid in the design of appropriate algorithms or schedules for insulin delivery.
“Normal” Insulin Secretion: The Goal of Artificial Insulin Delivery Systems?
Authors: Eaton R Philip , Allen Richard C , Schade David S , Standefer James C
Published: March 2007

Prehepatic insulin production can be determined from analysis of connecting-peptide behavior in the plasma. In the present study, we have determined prehepatic insulin production in six normal men throughout a day that included three typical 750-cal meals. Total insulin secretion for the 24 h was 45.4 ∪, secreted as 10.6 ∪ with breakfast, 13.4 ∪ with lunch, and 13.8 ∪ with dinner. The remaining 7.6 ∪ was secreted during the 9 h night at a rate of 0.85 ∪/h. At least 50% of the newly secreted insulin is known to be extracted by the liver during the initial transhepatic passage, so that total peripheral delivery can be estimated as approximately 22 ∪/day. Consequently, portal vein insulin levels are in excess of those seen in peripheral blood by at least 20 ± 8 μ∪/ml in the fasted state, and by as much as 115 ± 15 μ∪/ml in the 2-h postabsorptive state. The data suggest that insulinization of the liver, without peripheral hyperinsulinemia, may be a goal of artificial insulin delivery.
Electronic Flow Rate Controller for a Portable Insulin Infusion Pump
Authors: Ferguson R T , Zinman B , Marliss E B , Albisser A M
Published: March 2007

An electronic controller is described that regulates the flow of infusate by controlling the fraction of time that a pump is energized. Using the integral programming capability of the device, any one of 256 possible basal rates between 0 and 49.6% of the maximum rate can be chosen. An externally triggerable single meal-associated pulse can also be configured. The rate during the meal pulse can be any one of the 255 equally spaced rates in the range of 0–99.7%. The duration of this pulse can be chosen in 3-min steps to a maximum of 12.75 h, after which the rate automatically returns to the basal value. The controller consumes a minimum amount of power and can continuously operate a dc motor-driven pump at 3.0 V for 36 h. It drives the pump in an on-off mode in order to control the average flow rate digitally. In this way a significant reduction in the power requirements is realized and the system can be run for many days using small rechargeable batteries. One year of experience with 20 of these controllers was obtained in the research laboratory and clinical investigation unit. The results of this experience indicated the reliability and precision of these controllers, gave insight into their modes of failure, and provided valuable biomedical data for their improvement.
Some Engineering Aspects of Insulin Delivery Systems
Authors: Spencer W J , Bair R E , Carlson G A , Love J T , Urenda R S , Eaton R P , Schade D S
Published: March 2007

The characteristics of electronically controlled insulin delivery systems are presented. Early experiments with an external system have shown promise in providing improved glycemic control over conventional methods of single or multiple subcutaneous insulin injections. The encouraging results with external insulin delivery systems have led to the development and early testing in dogs of an implantable system with remote controls to permit variable insulin flow rates. A number of questions remain to be answered before widespread experimentation with external and implanted insulin delivery systems is possible. There appears to be no major development problems with the engineering aspects of such systems.
Clinical Features of Diabetes Mellitus in Japan
Authors: Baba Shigeaki , Morita Soichiro
Published: March 2007

The first Symposium on Diabetes Mellitus in Asia was held in Kobe, Japan, in 1970 and the second symposium in Kyoto, Japan, in 1975. These two symposia raised many questions. Participants from various countries compared their findings on the frequency of diabetes and its complications. Such comparisons are usually complicated because of the differences in diagnostic criteria used, the age groups compared, and duration of diabetes observed, etc. In spite of these problems, careful analysis and close comparisons may offer important clues as to the pathogenesis of diabetes and the factors related to its complications. Japanese and Caucasian diabetes have some differences resulting from the Japanese diabetic pathophysiologic, ethologic, and ecologic factors. In this paper, diabetes is discussed from an ecologic viewpoint, especially characteristics of the disease and its prognosis in relation to the complications and food habits in Japan.
Glycosylation of Variant Hemoglobins in Normal and Diabetic Subjects
Authors: Sosenko Jay M , Flückiger Rudolf , Platt Orah S , Gabbay Kenneth H
Published: March 2007

The extent of in vivo glycosylation of variant hemoglobins was examined in individuals with S-, C-, and D-trait. Chromatographie estimates of glycosylation for nondiabetic individuals with S-trait were significantly lower than those for nondiabetic black subjects with normal hemoglobin (P < 0.001). However, chemical determinations of glycosylation (thiobarbituric acid or TBA technique) were similar for these groups (P > 0.10). The Chromatographie elution pattern of hemoglobin S (HbS) was determined, and on this basis an adjustment procedure was performed for Chromatographie data. A regression line was calculated for the relationship between Chromatographie and colorimetrie estimates of glycosylated hemoglobin in S-trait individuals with and without diabetes. The slope of this line was significantly different (P < 0.001) from that for the relationship in individuals with normal hemoglobin. However, after adjustment of Chromatographie values from S-trait individuals, the slopes were similar (P > 0.10). Findings from individuals heterozygous for HbC and D were similar to those for individuals with S-trait. These data indicate that the extent of glycosylation of HbS, C, and D is similar to that of HbA in both the normoglycemic and hyperglycemic range. The TBA technique is the most direct method for determining the extent of glycosylation in individuals with HbS, C, or D. However, adjustment of column Chromatographie values is feasible.
Initiating Exercise Programs for Patients with Non-insulin-dependent Diabetes
Authors: Beeken Ruth K
Published: March 2007

Considerable attention has been focused on the importance of physical activity in improving the diabetic state in obese, non-insulin-dependent diabetic patients. Because this patient population tends to be sedentary, this challenge requires an active effort involving the patient and health-care providers. The latter may be a team including physician, dietitian, nurse practitioner, and physical therapist. Programs must be individualized. The patient must be a full partner in developing plans and goals. Plans should represent the patient's interests, should blend into the daily schedule, and should avoid boredom. Programs are adapted to the patient's physical condition and are graduated in duration and intensity. Motivation is stimulated through education and is reinforced both by self-monitoring techniques and monitoring by providers. Such programs add a new dimension to both physical and psychological well-being.
Improved Control in Diabetes with Continuous Subcutaneous Insulin Infusion
Authors: Schiffrin Alicia , Colle Eleanor , Belmonte Mimi
Published: March 2007

Nine insulin-dependent diabetic patients were treated with continuous subcutaneous (s.c.) insulin infusion, using a portable battery-driven infusion pump and home monitoring of capillary blood glucose. The infusions were maintained for 4 days during an acute in-hospital study and for up to 150 days on ambulatory patients. No significant changes in growth hormone and cortisol secretory patterns were found at the end of the acute study. Mean plasma glucose, M values, and glycosylated hemoglobin A1 (HbA1), as well as the patients' sense of well-being, improved significantly. However, absolute normalization of metabolic control was not achieved, since patients presented occasional, albeit minor, swings of blood glucose. The possibility that the same improvement in control could be achieved with multiple s.c. injections of insulin and similar monitoring of blood glucose in the home is discussed. It remains to be seen whether the degree of control obtained will influence the development of the late complications of diabetes mellitUS.
Relationships Between Control and Serum Lipids in Juvenile-onset Diabetes
Authors: Glasgow Allen M , August Gilbert P , Hung Wellington
Published: March 2007

The relationship between control and serum lipids was examined in 147 children with juvenile-onset diabetes (JOD). Control was assessed by fasting blood glucose, 24-h urine glucose, and fast hemoglobin. There was a significant positive correlation (P < 0.001) between each of the measures of control. Serum cholesterol (P < 0.001), triglycerides (P < 0.001), and low-density lipoprotein plus very low-density lipoprotein cholesterol (P < 0.001) were strongly positively correlated with control for the whole group of patients. High-density lipoprotein was not significantly correlated with control when the data for the whole group were analyzed but was significantly positively correlated with fasting blood glucose when patients were analyzed individually.
Immunologic Properties of Biosynthetic Human Insulin in Vitro
Authors: Beischer W , Maier V , Jonatha E M , Hartweg D , Kratzsch G
Published: March 2007

Some immunologic properties of biosynthetic human insulin (BHI) were examined in vitro. An identical behavior was found for BHI and pancreatic human insulin as standard preparation and for A14-mono-labeled BHI and pork insulin as tracer in the insulin radioimmunoassay. BHI proved to be free of human proinsulin and C-peptide. Insulin antibodies in serum of two diabetic patients showed a preferential binding of 125I-bovine insulin. However, the antibody titers were almost identical for A14-mono-labeled BHI and pork insulin. These studies did not reveal any characteristic immunologic properties of BHI compared with highly purified pancreatic human and pork insulin.
Studies on the Biologic Actions of Biosynthetic Human Insulin In Vitro and in Diabetic Man
Authors: Waldhäusl Werner K , Kastner Gerhard , Komjati Martin , Bratusch-Marrain Paul
Published: March 2007

This preliminary study was designed to determine whether biologic action of biosynthetic human insulin (BHI) in vitro and its antigenicity in man equals that of various insulins of pancreatic origin. Testing the biologic action of BHI, pancreatic human insulin (PHI), and pancreatic pork insulin (PCPI) on glucose uptake by the rat hemidiaphragm and adipose tissue, identical efficacy for the insulins on a unit per unit basis was observed. Furthermore, a comparable impairment of insulin action was seen under the detrimental conditions of a hyperosmolal state. In an insulin-dependent diabetic female patient with cutaneous insulin hypersensitivity, BHI displayed the same antigenicity as PHI and PCPI. From these data we conclude tht BHI, both in vitro and in vivo, exhibits the same biologic properties as pancreatic insulin, and that it is reasonable to continue extensive testing of BHI in man, since identical metabolic effects and immunologic reactions are to be anticipated as with purified pancreatic insulin preparations of human or animal origin.
Receptor Binding of Biosynthetic Human Insulin on Isolated Pig Hepatocytes
Authors: Gammeltoft Steen
Published: March 2007

Biosynthetic human insulin (BHI) and pancreatic human insulin were compared with respect to receptor binding in a heterologous assay system: displacement of pork A14-125I-monoiodoinsulin from receptors on pig hepatocytes. The concentrations of human insulin giving half-maximal displacement were identical for both preparations, i.e., 0.5 nM. Their relative potency was 1.01 ± 0.14 (SD, N = 5), suggesting that biosynthetic and pancreatic human insulin exert the same biologic activity.
Binding of Biosynthetic Human Insulin to Human Antibodies and Receptors
Authors: Petersen KG , Schlüter K , Steinhilber S , Kerp L
Published: March 2007

The binding of biosynthetic human insulin (BHI) and pork insulin to anti-pork insulin antibodies was tested at an insulin concentration of 4 μU/ml. Identical binding data were obtained. The binding of the two insulins to mononuclear lymphocytes was also identical. The data are compared to previous results obtained with synthetic human insulin. Previously, we investigated the in vitro properties of fully synthetic human insulin from Dr. Rittel, Ciba-Geigy, Base.1 Receptor binding of this human insulin was identical to pork insulin. The binding properties of the new BHI from Lilly (Indianapolis) were studied with human antibodies and freshly isolated human monocytes.
The Biologic Potency and Binding Affinity of Biosynthetic Human Insulin in Isolated Rat Adipocytes
Authors: Sonne Ole , Foley James E , Gliemann Jørgen
Published: March 2007

Using the isolated rat adipocyte system, we could not detect any difference in binding affinity or biologic potency of biosynthetic and pancreatic human insulin.
Binding of Insulin to Rat Pancreatic Islets: Comparison Between Pancreatic Human Insulin and Biosynthetic Human Insulin
Authors: Verspohl E J , Ammon H P T
Published: March 2007

Human pancreatic insulin, biosynthetic human insulin (BHI), and pork insulin were compared in terms of their binding characteristics to insulin receptors on rat pancreatic islets. There was no difference in binding or on biologic effect, i.e., ability to inhibit insulin secretion.
Receptor Binding and Effect of Biosynthetic Human Insulin on 2-Deoxyglucose Transport
Authors: Wieringa Tj , Van Putten J P M , Van Dijk-Besling M , Krans H M J
Published: March 2007

Biosynthetic human insulin (BHI) and purified pork insulin (PPI) were compared for binding properties and stimulatory effect on 2-deoxyglucose transport in isolated rat fat cells. No difference between these types of insulin could be demonstrated.
Comparison of Pancreatic Human and Biosynthetic Human Insulin with Respect to Their Action on Adipocytes and Chick Embryo Fibroblasts
Authors: Zapf J , Froesch E R
Published: March 2007

Biosynthetic human insulin (BHI) was compared to pancreatic human insulin and sperm whale insulin in terms of ability to stimulate incorporation of glucose into isolated rat adipocytes and thymidine into DNA in chick embryo fibroblasts. The human insulins were identical in their effects in both assays. Sperm whale insulin was more potent than the human insulins in stimulating glucose incorporation into rat adipocytes. All three insulins showed identical stimulation of DNA synthesis in the fibroblast assay. That action, however, is mediated via the receptor for insulin-like growth factor (IGF-I). Therefore, both human insulins were evaluated in terms of binding to the IGF-1 receptor in chick embryo fibroblasts. The two human insulins behaved identically (and agreed with previous findings for sperm whale insulin). All insulins, however, were approximately 200-fold less potent than IGF-I itself in this binding assay.
Long-Term, Ambulatory, Subcutaneous Insulin Infusion versus Multiple Daily Injections in Brittle Diabetic Patients
Authors: Barbosa Jose , Menth Lois , Eaton John , Sutherland David , Freier Esther F , Najarian John
Published: March 2007

We compared the blood glucose control of four intact and eight kidney recipient, metabolically unstable, ketosis-prone, insulin-dependent diabetic patients under two different regimens: (a) intensive conventional treatment with two to four insulin injections daily (48 patient-months) and (B) subcutaneous, portable insulin delivery system (IDS) (54 patient-months). Both regimens included frequent home blood glucose and 24-h urine glucose determinations and daily telephone follow-up to maximize compliance with treatment. Analyzed as a group the fasting blood glucose for intact patients (A: 172 ± 13 mg/dl; B: 141 ± 12, P < 0.02) and the nonfasting blood glucose for kidney recipient patients (A: 165 ± 10; B: 138 ± 5, P < 0.01) were significantly lower during treatment with the IDS than with multiple injections. Six out of 12 patients (2/4 intact and 4/8 kidney recipient patients) showed significant and consistent improvement of blood glucose concentrations. Four showed marginal and inconsistent improvement. Two patients (one intact and one kidney recipient) improved on the IDS but maintained the improvement when changed back to conventional treatment. The 24-h urine glucose, maximal glucose excursions, number of blood glucoses ≤ 40 mg/dl, and glycosylated hemoglobin decreased significantly in some patients on the pump. We conclude that subcutaneous, portable insulin delivery devices can significantly improve the metabolic control of some ambulatory, unstable diabetic patients during long-term treatment beyond that obtained with intensive, multiple-injection, conventional treatment. Normalization of the metabolic control, however, is not obtained. These infusion systems still pose several problems during ambulatory use, which could have serious consequences in patients less compliant and/or followed less closely than ours.
Relief of Gastrointestinal Symptoms by Correcting Insulin Excess
Authors: Riddle Matthew C
Published: March 2007

Persons with diabetes mellitus often have disordered gastrointestinal function, usually attributed to autonomic neuropathy. Hypoglycemia in persons taking insulin has been considered a possible result of anorexia and gastric atony, but not a potential cause of gastrointestinal symptoms. Three patients with diabetes developing before age 30 yr and of long duration had severe gastrointestinal complaints for 1–9 mo, with symptoms suggesting nocturnal hypoglycemia. All recovered rapidly with no specific treatment other than reduction of insulin doses. Studies identified no gastrointestinal pathology. These patients may represent a subgroup of persons with diabetic enteropathy, in whom recurrent hypoglycemia provokes a reversible derangement of gut function with accompanying symptoms.
Recovery from Decompensated Non-insulin-dependent Diabetes Mellitus: Studies of C-Peptide Secretion
Authors: Rendell Marc , Zarriello Joan , Drew Helen Mikesell , Dranbauer Barbara , Wilson Gregory , Waud John , Ross David
Published: March 2007

Eleven non-insulin-dependent diabetic patients presented with decompensated hyperglycemia. Nine had pronounced ketonuria, five with acidosis. In seven cases, precipitating factors were identified. In the other four cases, including three cases of diabetic ketoacidosis, no identifiable triggering events were present. In each case, recovery from the initially decompensated diabetic state occurred. Eventually, all patients were managed by diet alone. Seven patients demonstrated nondiabetic glucose tolerance tests (GTT). Several patients underwent stressful situations after “recovery” without recurrence of hyperglycemia. Glucose-stimulated C-peptide levels were determined postrecovery. C-peptide secretion was in the normal range and, in fact, was identical, in relation to glucose levels, to that in a group of nondiabetic volunteers. In 6 of the 11 cases, C-peptide secretion was measured at the time of initial presentation. These levels were markedly lower than comparable values during the GTT postrecovery. Non-insulin-dependent diabetes, even when presenting in a decompensated state, is subject to a considerable degree of reversibility and even recovery to a nondiabetic state in some cases. Recovery is associated with a return to normal C-peptide secretion.
Improving Survival After Renal Transplantation for Diabetic Patients with Severe Coronary Artery Disease
Authors: D'Elia John A , Weinrauch Larry A , Kaldany Antoine , Libertino John A , Leland O Stevens , Healy Robert W , Miller Donald G
Published: March 2007

After successful renal transplantation, seven diabetic renal failure patients with severe coronary artery disease returned to productive employment. Despite the requirement for additional peripheral vascular or ophthalmologic surgery in four patients, their renal function remained adequate. Following transplantation, diabetic complications included angina in three, myocardial infarction in three, and cerebrovascular accident in two patients. Two patients with adequate renal function died suddenly at 29 and 62 mo. Despite severe coronary artery disease, an increasing number of diabetic dialysis patients may be able to return to work after a successful kidney transplant.
Stability of Reacted Reagent Strips (Chemstrips) for Blood Glucose Determinations
Authors: Kubilis Paul , Rosenbloom Arlan L , Cimino Pat , Rosenbloom Eric D
Published: March 2007

Reacted Chemstrips were placed in an unsealed envelope or in desiccator vials which were opened daily after 1, 2, 3, 4, 5, 6, 7, and 14 days. The time of change of the reading for 2 days in a row by all three observers was noted. Readings in the low and normal range were most stable and can be considered reliable for 2–3 days when protected from light. If in a desiccator tube, the strips can be reliably reread when the tube is opened as long as 7 days later. In a separate study, strips were left exposed on the laboratory bench or placed in a vial and read frequently for 6 h and again at 28 h. This exposure, comparable to the CS being taped to a hospital record, results in reading changes as early as 2 h after reaction.
Hemoglobin A1 Properties of Diabetic and Uremic Patients
Authors: Oimomi Munetada , Yoshimura Yukio , Kubota Shinzo , Kawasaki Tomiyasu , Takagi Kiyoshi , Baba Shigeaki
Published: March 2007

Patients with diabetes mellitus as well as those with renal failure had high hemoglobin A1 (HbA1) levels. However, the portion of HbA1a+b fractions was larger in patients with renal failure than in diabetic patients. Thus, if renal disorder is advanced, caution should be exercised in evaluating HbA1 data. Furthermore, not only is the collective determination of Hb minor components such as HbA1 required, but also investigation of changes in HbA1a+b in patients with renal failure or diabetic nephropathy.
Epidemiology of Diabetes Mellitus in Prince Edward Island
Authors: Tan Meng H , Wornell M Charleen , Beck Angus W
Published: March 2007

In Prince Edward Island, all diabetic inhabitants who register annually with the Provincial Department of Health can obtain prescribed hypoglycemic medications and urine testing materials free of charge. Since 1964, this drug program has served as an informal register of the diabetic patients living on the island. Based on the data available, the following observations are made: (1) The prevalence rate of diabetes increased from 0.89% in 1966 to 1.53% in 1977. The prevalence rates increased from 0.05% in the <9-yr age group to 8.4% in the >90-yr age group. The prevalence rate of diabetes among school children was 0.19%. (2) The incidence rate was 1.89/1000 in 1977. The highest incidence rate was in the >40-yr age group and the lowest in the < 10-yr age group. (3) Fourteen and a half percent of the diabetic persons were treated with diet alone, 52.7% with oral agents, and 32.5% with insulin in 1977. (4) In 1978, the cost per diabetic person for providing benefits was: oral agent = $14.88, insulin = $84.75, urine testing materials = $9.29, and education = $38.08.
Urine Cortisol/Creatinine Ratio in Controlled Insulin-induced Hypoglycemia
Authors: Seaworth John F , Seaworth Barbara J , Jordan Richard M
Published: March 2007

An elevated urine cortisol/creatinine ratio has been presented as a simple laboratory method to detect nocturnal hypoglycemia. The present study examines the time course of the rise and fall of the urine cortisol/creatinine ratio in 11 patients following insulin-induced hypoglycemia. The mean urine cortisol/ creatinine ratios at 1 and 3 h after the onset of symptomatic hypoglycemia were 170 ± 103 and 62 ± 23, respectively. These were significantly greater (P < 0.01) than the basal ratio of 13 ± 7. By 5 h, the ratio had fallen to 19 ± 11, which was similar to basal values. The study documents the sensitivity of the urine cortisol/creatinine ratio in detecting hypoglycemia but indicates that after 3 h, the ratio may return to normal despite a previous hypoglycemic episode.