bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired Left Ventricular Diastolic Function and Vascular Postischemic Vasodilation Associated with Microalbuminuria in IDDM Patients
Authors: Guglielmi Maria D , Pierdomenico Sante D , Salvatore Luigi , Romano Ferdinando , Tascione Evandro , Pupillo Mario , Porreca Ettore , Imbastaro Tiziana , Cuccurullo Franco , Mezzetti Andrea
Published: March 2007

OBJECTIVE

Microalbuminuria is considered an important predictor of cardiovascular events in diabetic patients. In this study, a possible association of microalbuminuria with significant changes in left ventricular (LV) morphology and function and generalized vascular dysfunction was analyzed in insulin-dependent diabetes mellitus (IDDM) patients without hypertension, coronary artery disease, or autonomie dysfunction.

RESEARCH DESIGN AND METHODS

Thirty-four young long-term IDDM patients, 16 with and 18 without microalbuminuria, and 20 control subjects were studied. LV systolic function and wall thickness were evaluated by M-mode echocardiography. LV diastolic function was studied using a combined echo-Doppler and phonocardiographic technique. The hyperemic response to forearm ischemia was measured by strain-gauge plethysmography. All patients underwent 24-h ambulatory blood pressure monitoring.

RESULTS

LV mass index and wall thickness:radius ratio were significantly higher in microalbuminuric patients. LV relaxation was significantly impaired in both diabetic groups compared with control subjects; moreover, this impairment was significantly greater in microalbuminuric than in normoalbuminuric patients. In microalbuminuric patients, forearm postischemic vasodilation was also significantly lower and mean awake diastolic blood pressure (dBP) was significantly higher than in the other two groups.

CONCLUSIONS

Our data suggest that microalbuminuria is associated with significant changes in LV morphology, a more severe impairment of cardiac diastolic function, altered vascular dilatory capacity, and higher daytime dBP. Therefore, microalbuminuric patients should be considered to have a higher risk of cardiovascular complications and be kept under closer surveillance.
A Call for Specific Codes for Diabetes Foot and Eye Care
Authors: Mayfield Jennifer A , Strand Timothy , Toya Al R
Published: March 2007

In this report, we propose new International Classification of Diseases (ICD) codes that could be incorporated into computer-based patient records or administrative data to monitor and improve diabetes care. Neither the ICD, 9th Revision, nor its imminent replacement, the ICD, 10th Revision, has specific codes for foot examinations and funduscopic examinations in the asymptomatic person, high-risk diabetic foot status, or clinically significant macular edema. Adoption of official codes for these procedures and conditions implemented in conjunction with computerized databases could be used for surveillance, program planning, and quality of care assessment. Computerized medical records could use the codes to monitor care and issue reminders to patients and providers. Payors could offer reimbursement incentives to encourage compliance with standard recommendations. These codesfor care procedures could be linked to outcomes, such as amputations and blindness, to improve our understanding of the etiology of blindness and the relationship between processand outcome. The uniform adoption of these codes would facilitate comparison between health care systems, geographic regions, and nations. The diabetes community should encouragethe National Center for Health Statistics to adopt new codes that could be used to monitor diabetes preventive care practices.
Apolipoprotein E Polymorphism as a Risk Factor for Vascular Disease in Diabetic Patients
Authors: Boemi Massimo , Sirolla Cristina , Amadio Loredana , Fumelli Paolo , Pometta Daniel , James Richard W
Published: March 2007

OBJECTIVE

To examine the prevalence of cardiovascular disease in diabetic patients as a function of apolipoprotein (apo) E polymorphism.

RESEARCH DESIGN AND METHODS

The apo E phenotypes and plasma lipid, lipoprotein, and apo levels were determined for 517 Italian diabetic patients. The prevalence of cardiovascular disease (defined as ischemic heart disease [IHD] and/or peripheral vascular disease and/or cerebrovascular disease) was assessed as a function of apo E polymorphism at entry and after 4 years.

RESULTS

The occurrence of vascular disease did not differ significantly between diabetic patients in the various categories of apo E phenotype either at entry into the study or after 4 years. When expressed as a percentage of patients with disease, we observed—for E2, E3, and E4 carriers, respectively—at entry: IHD, 20.0% (n = 14), 21.0% (n = 79), and 21.5% (n = 14); and macroangiopathy, 24.3% (n = 17), 29.3% (n = 110), and 24.6% (n = 16). Apo E polymorphism did not make a significant contribution to multiple logistic regression models designed to identify the factors associated with the occurrence of vascular disease in diabetic patients.

CONCLUSION

Apo E polymorphism and, notably, the apo E4 allele cannot be universally considered as a particular risk factor for cardiovascular disease in diabetic patients.
A Multicenter Evaluation of Blood Glucose Awareness Training-II
Authors: Cox Daniel , Gonder-Frederick Linda , Polonsky William , Schlundt David , Julian Diana , Clarke William
Published: March 2007

OBJECTIVE

Blood glucose awareness training (BGAT) teaches individuals with insulin-dependent diabetes to more accurately estimate/detect their blood glucose (BG) fluctuations. It has not, however, consistently resulted in improved ability to detect low BG. To assess an enhanced version of BGAT (BGAT-II), with more focus on increasing sensitivity to low BG events, a multicenter study was undertaken. Following up on previous findings that BGAT is most effective with individuals who are least accurate in estimating BG, this study explicitly recruited subjects who did and did not report reduced awareness of hypoglycemia.

RESEARCH DESIGN AND METHODS

Seventy-eight subjects from three research sites participated in a repeated baseline design. Subjects' BG estimation accuracy and BG profiles were assessed 6 months before, immediately before, and immediately after BGAT-II.

RESULTS

Post-treatment, BGAT-II led to better overall accuracy in detecting BG fluctuations and better detection of both low and high BG levels. This was achieved while the number of low readings of self-monitoring of blood glucose (SMBG) was reduced. Reduction in the number of low SMBG events was significant only for subjects reporting awareness of hypoglycemia. Detection of low BG was significant only for subjects reporting reduced awareness of hypoglycemia. Both groups demonstrated equivalent improvements in detection of high BG levels.

CONCLUSIONS

BGAT may be an eﬀective behavioral strategy for reversing hypoglycemic unawareness and an adjunct to intensive insulin therapy to reduce the occurrence of severe hypoglycemia.
Hypoglycemm Increases the Gastric Emptying Rate in Healthy Subjects
Authors: Schvarcz Erik , Palmér Mats , Åman Jan , Berne Christian
Published: March 2007

OBJECTIVES

To compare the gastric emptying rate during normoglycemia with that during insulin-induced hypoglycemia in healthy subjects.

RESEARCH DESIGN AND METHODS

In eight healthy subjects, the rate of gastric emptying of an isotope-labeled meal was assessed by a scintigraphic technique during normoglycemia and hypoglycemia, both controlled by an insulin-glucose clamp.

RESULTS

The mean time taken to empty 50% of the test meal from the stomach (Tg0) for the solid phase was 43.0 ± 20.0 min during normoglycemia, compared with 16.3 ± 6.6 min during hypoglycemia, P < 0.001. The mean T50 for the liquid phase was 38.0 ± 21.2 and 15.4 ± 10.6 min, respectively, P < 0.001.

CONCLUSIONS

Insulin-induced hypoglycemia increases the gastric emptying rate in healthy subjects.
Earlier Appearance of Impaired Insulin Secretion Than of Visceral Adiposity in the Pathogenesis of NIDDM: 5-Year Follow-up of Initially Nondiabetic Japanese-American Men
Authors: Chen Kwang-Wen , Boyko Edward J , Bergstrom Richard W , Leonetti Donna L , Newell-Morris Laura , Wahl Patricia W , Fujimoto Wilfred Y
Published: March 2007

OBJECTIVE

To identify risk factors for development of non-insulin-dependent diabetes mellitus (NIDDM) during a 5-year longitudinal follow-up of second-generation Japanese-American (Nisei) men.

RESEARCH DESIGN AND METHODS

For 5 years, 137 initially nondiabetic Nisei men were followed with 75-g oral glucose tolerance tests at the initial visit and at 2.5- and 5-year follow-up visits. Body fat distribution was assessed by computed tomography (CT) and body mass index (BMI) calculated at each visit. Fasting insulin and C-peptide, the increment of insulin and C-peptide at 30 min after the oral glucose load, intra-abdominal and total subcutaneous fat by CT, and BMI were compared between those who remained nondiabetic (non-DM) and those who had developed NIDDM at 2.5 years (DM-A) and 5 years (DM-B).

RESULTS

At baseline, the DM-A group had significantly increased intra-abdominal fat, elevated fasting plasma C-peptide, and lower C-peptide response at 30 min after oral glucose. At the 2.5-year follow-up, this group had markedly increased fasting plasma insulin and decreased 30-min insulin and C-peptide response to oral glucose. The DM-B group also had significantly lower insulin response at 30 min after oral glucose at baseline but no significant difference in intra-abdominal fat or fasting plasma insulin and C-peptide levels. When this group developed NIDDM by 5-year follow-up, however, an increase of intra-abdominal fat was found superimposed on the pre-existing lower insulin response. Fasting plasma insulin and C-peptide remained low.

CONCLUSION

In DM-A, lower 30-min insulin response to oral glucose (an indicator of β-cell lesion) and increased intra-abdominal fat and fasting C-peptide (indicators of insulin resistance) were the risk factors related to the development of NIDDM. DM-B subjects had a lower 30-min insulin response to oral glucose at baseline and increased intra-abdominal fat at 5-years, when they were found to have NIDDM. Thus, both insulin resistance and impaired β-cell function contribute to the development of NIDDM in Japanese-Americans, and impaired β-cell function may be present earlier than visceral adiposity in some who subsequently develop NIDDM.
The Relationship Between Smoking and Microvascular Complications in the EURODIAB IDDM Complications Study
Authors: Chaturvedi Nishi , Stephenson Judith M , Fuller John H ,   The EURODIAB IDDM Complications Study Group
Published: March 2007

OBJECTIVE

To examine the relationship between smoking and both glycemic control and microvascular complications in patients with insulin-dependent diabetes mellitus (IDDM).

RESEARCH DESIGN AND METHODS

This was a prevalence survey of 3,250 men and women aged 15–60 years with IDDM from 31 diabetes centers in 16 European countries. Participants completed a questionnaire, had retinal photographs taken, and performed a 24-h urine collection. HbA1c, frequency of hypoglycemic and ketoacidotic episodes, urinary albumin excretion rates, and retinopathy were compared by smoking category.

RESULTS

The prevalence of smoking was 35% in men and 29% in women. Current smokers had poorer glycemic control and, among men, were more likely to have had a ketoacidotic episode than were those who never smoked. Ex-smokers had equivalent glycemic control and marginally more hypoglycemic episodes did than those who never smoked. Current smokers had a higher prevalence of microalbuminuria and total retinopathy than did those who never smoked. Ex-smokers had a higher prevalence of macroalbuminuria and proliferative retinopathy than did those who never smoked, but both had a similar prevalence of microalbuminuria. Adjustment for either current or long-term glycemic control could not fully account for these differences.

CONCLUSIONS

Smoking is associated with poorer glycemic control and an increased prevalence of microvascular complications compared with not smoking. Ex-smokers can achieve glycemic control equivalent to and have a prevalence of early complications similar to that of those who never smoked. We suggest that poorer glycemic control can account for some of the increased risk of complications in smokers, and that quitting smoking would be effective in reducing the incidence of complications. Urgent action is required to reduce the high smoking rates in people with IDDM.
Hormonal Contraception in Women With IDDM: Influence on glycometabolic control and lipoprotein metabolism
Authors: Petersen Kresten R , Skouby Sven O , Vedel Pernille , Haaber Anne B
Published: March 2007

OBJECTIVE

Safe and effective contraceptive methods are essential for women with insulin-dependent diabetes mellitus (IDDM), but opinions on the use of hormonal oral contraceptives by these women are conflicting. We evaluated the effects on glycometabolic control and lipoprotein metabolism in women with IDDM treated with an oral contraceptive not previously studied in a diabetic population.

RESEARCH DESIGN AND METHODS

A total of 22 women with IDDM received a monophasic combination of ethinyl estradiol and gestodene for 1 year; 20 women of comparable diabetic status using nonhormonal contraception were selected as control subjects. Evaluation was performed before and after 1, 3, 6, and 12 months of hormonal intake using nonparametric statistical methods.

RESULTS

Except for a higher median age of the control group, the baseline values for all clinical and metabolic variables were similar in the two groups, and in neither of the groups were changes in blood pressure, body mass index, or glycemic control observed. In the oral contraceptive group, decreased serum levels of low-density lipoprotein (LDL) cholesterol and increased levels of triglycerides and lipoprotein A were noted, whereas total cholesterol and high-density lipoprotein cholesterol levels were unchanged. In the control group, a decrease of LDL cholesterol was observed. No effect of tobacco smoking on glycometabolic control or lipoprotein metabolism could be demonstrated during hormonal intake.

CONCLUSIONS

No evidence of impaired glycometabolic control or adverse changes in serum levels of lipoproteins known to be associated with atherosclerosis was observed in women with well-controlled IDDM during 1 year of oral contraception with ethinyl estradiol and gestodene.
IDDM in the Province of Pavia, Italy, From a Population-Based Registry: A descriptive study
Authors: Tenconi Meria T , Devoti Gabriele , Albani Ileana , Lorini Renata , Martinetti Miryam , Fratino Pietro , Ferrari Ettore , Ferrero Enrico , Severi Francesca
Published: March 2007

OBJECTIVE

To report the incidence of insulin-dependent diabetes mellitus (IDDM) in the Province of Pavia, Italy, in the 0- to 29-year-old age-group between 1988 and 1992. Urban versus rural residence, socioeconomic level, and family size of IDDM cases were also investigated.

RESEARCH DESIGN AND METHODS

A prospective register was established in 1988 to collect all newly diagnosed IDDM patients with onset before 30 years of age. The primary data source was based on notification of new cases by hospitals, out-patient clinics, family doctors, and pediatricians. The secondary and independent data source consisted of the registries of prescriptions for insulin syringes in the health districts of the province.

RESULTS

In 5 years (1988–1992), 66 cases of IDDM in the 0- to 29-year-old age-group were identified. The completeness of ascertainment was 100% for the combined sources. Age-adjusted (world-standardized) incidence rates per 100,000 (95% confidence interval) were 9.52 (6.42–13.61), 6.72 (4.68–9.34), and 8.27 (6.42–10.58), respectively, for the age-groups 0–14, 15–29, and 0–29. The rates were higher for residents in urban areas. The number of children in the families of IDDM patients was significantly higher than in the reference population.

CONCLUSIONS

Our data indicate the concordance of IDDM incidence rates with the North-Italian rates and a possible association of the disease with environmental factors. These factors might enhance the susceptibility to IDDM in genetically predisposed individuals.
Association Between Lipoprotein(a) and Insulin-Like Growth Factor I During Puberty and the Relationship to Microalbuminuria in Children and Adolescents With IDDM
Authors: Rudberg Susanne , Persson Bengt
Published: March 2007

OBJECTIVE

To study pubertal changes in serum lipoprotein(a) [Lp(a)] and insulin-like growth factor I (IGF-I) in insulin-dependent diabetes mellitus (IDDM) and the relationship to microalbuminuria.

RESEARCH DESIGN AND METHODS

Seventy-nine children and adolescents (59 with normoalbuminuria, 20 with microalbuminuria) with ≥ 5 years of IDDM were investigated together with 54 healthy control subjects in a cross-sectional study. Fasting serum Lp(a); apolipoprotein (apo) A-1 and B; total, low-density lipoprotein (LDL), and high-density lipoprotein cholesterol; triglycerides; and IGF-I were analyzed as were HbA1c and overnight albumin excretion rate (AER). Pubertal development was assessed by Tanner staging.

RESULTS

Lp(a), apoB, triglycerides, and total and LDL cholesterol were higher (P < 0.001) and apoA-1 was lower (P = 0.03) in normoalbuminuric IDDM patients than in healthy control subjects. Lp(a) was increased during puberty (stages 2–4) in IDDM patients but not in healthy subjects, whereas IGF-I was significantly increased during puberty in healthy control subjects only. In IDDM patients Lp(a) correlated to insulin dose, total cholesterol, and LDL cholesterol, but not to IGF-I, HbA1c, systolic and diastolic blood pressure, diabetes duration, age, or sex. In multiple regression analysis with Lp(a) as the dependent variable, puberty was the only significant contributor to the regression (r2 = 0.33, P = 0.008). Microalbuminuria was seen only in the pubertal stage 4–5. Lp(a) tended to be higher (P = 0.06) as did apoB, whereas IGF-I was lower (P < 0.001) in this group than in normoalbuminuric patients of the same pubertal stages. In multivariate analysis, with log AER as the dependent variable, apoB/apoA-1, systolic blood pressure, age, and IGF-I but not Lp(a) added to the regression (r2 = 0.47, P < 0.0001).

CONCLUSIONS

Lp(a) is elevated during puberty in normoalbuminuric subjects with IDDM, independent of metabolic control and IGF-I. Lp(a) tends to be further increased in microalbuminuria but does not seem to be a contributing determinant of log AER whereas low IGF-I does. Prospective studies are required to establish the temporal relationship between increased Lp(a) and microalbuminuria in children and adolescents with IDDM.
Antibodies Against Bovine Albumin and Other Diabetes Markers in French Children
Authors: Lévy-Marchal Claire , Karjalainen Jukka , Dubois Frédéric , Karges Wolfram , Czernichow Paul , Dosch Hans-Michael
Published: March 2007

OBJECTIVE

Findings in epidemiology and animal experimentation suggest that autoimmunity in insulin-dependent diabetes mellitus (IDDM) may be triggered by dietary cow-milk protein, particularly bovine serum albumin (BSA). Elevated IgG anti-BSA antibodies were found in children from Finland with newly onset diabetes; Finland has the highest incidence of diabetes and cow's milk consumption in the world. We now analyze BSA serology and other diabetes markers in school-age children from France, where diabetes incidence and cow's milk consumption are low.

RESEARCH DESIGN

Sera were obtained from three groups: newly diagnosed diabetic (n = 43), islet cell antibody-positive (ICA+) nondiabetic (n = 98), and ICA− healthy control children (n = 267). IgG anti-BSA antibody levels were measured blindly using particle concentration fluoroimmunoassays and analyzed in comparison with ICA titers and human leukocyte antigen-DQB genotypes.

RESULTS

There were highly significant differences in BSA antibody levels between all three groups (P < 0.0001). Diabetic patients had elevated anti-BSA levels in 74.4% of cases, compared with 5.5% of control children. In the group of ICA+ non-diabetic children, 20% were anti-BSA-positive. Neither ICA nor BSA antibody titers were significantly related to DQB genotype or sex. ICA titers (≥4 Juvenile Diabetes Foundation units) were present in 84% of diabetic children. Two-thirds of diabetic children were positive for both ICA and anti-BSA antibodies, and none were negative for both markers.

CONCLUSIONS

Elevated IgG anti-BSA levels are associated with IDDM in the low-incidence French population. In newly diagnosed diabetic children, these antibodies have similar specificity (95 vs. 98%) and slightly lower sensitivity for IDDM than ICA (74.4 vs. 83.7%). Our results may support an immunological role of BSA in diabetic autoimmunity.
Serum Sialic Acid Concentration and Coronary Heart Disease in NIDDM
Authors: Pickup John C , Mattock Martin B , Crook Martin A , Chusney Gary D , Burt Davina , Fitzgerald Anthony P
Published: March 2007

OBJECTIVE

To examine the association between serum sialic acid concentrations and coronary heart disease (CHD) in a cross-sectional study of non-insulin-dependent diabetes mellitus (NIDDM).

RESEARCH DESIGN AND METHODS

NIDDM patients (n = 145) attending a diabetic clinic were studied. CHD status was assessed by questionnaire and electrocardiogram coding, and potential risk factor assessment included measurement of fasting serum lipid and lipoprotein concentrations, blood pressure, and urinary albumin excretion rate (AER).

RESULTS

Male NIDDM patients with CHD had a higher serum sialic acid level than those without CHD: 2.56 (2.24, 2.72) mmol/l vs. 2.24 (2.18, 2.30) mmol/l, P = 0.01, mean (95% confidence interval). They were also older, had a longer duration of diabetes, had a higher AER, had higher total triglyceride, very-low-density lipoprotein triglyceride and cholesterol, and lipoprotein(a) concentrations, and had a lower apolipoprotein A1 concentration. In an age adjusted multiple lipoprotein(a), hypercholesterolemia, and hypertension were associated with CHD. In women, only hypertension treatment was associated with CHD.

CONCLUSIONS

There is a strong univariate association between elevated serum sialic acid and CHD in men (but not women) with NIDDM.
Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VA CSDM): Results of the feasibility trial
Authors: Abraira Carlos , Colwell John A , Nuttall Frank Q , Sawin Clark T , Nagel Nancy Johnson , Comstock John P , Emanuele Nicholas V , Levin Seymour R , Henderson William , Lee Hae Sook ,   VA CSDM Group
Published: March 2007

OBJECTIVE

It is not clear whether intensive pharmacological therapy can be effectively sustained in non-insulin-dependent diabetes mellitus (NIDDM). The relative risks and benefits of intensive insulin therapy in NIDDM are not well defined. Accordingly, we designed a feasibility study that compared standard therapy and intensive therapy in a group of NIDDM men who required insulin due to sustained hyperglycemia.

RESEARCH DESIGN AND METHODS

A prospective trial was conducted in five medical centers in 153 men of 60 ± 6 years of age who had a known diagnosis of diabetes for 7.8 ± 4 years. They were randomly assigned to a standard insulin treatment group (one morning injection per day) or to an intensive therapy group designed to attain near-normal glycemia and a clinically significant separation of glycohemoglobin from the standard arm. A four-step plan was used in the intensive therapy group along with daily self-monitoring of glucose: 1) an evening insulin injection, 2) the same injection adding daytime glipizide, 3) two injections of insulin alone, and 4) multiple daily injections. Patient accrual and adherence, glycohemoglobin (HbA1c), side effects, and measurements of endpoints for a prospective long-term trial were assessed.

RESULTS

Accrual goals were met, mean follow-up time was 27 months (range 18–35 months), and patients kept 98.6% of scheduled visits. After 6 months, the mean HbA1c in the intensive therapy group was at or below 7.3% and remained 2% lower than the standard group for the duration of the trial. Most of the decrease in the mean HbA1c in the intensive group was obtained by a single injection of evening intermediate insulin, alone or with daytime glipizide. By the end of the trial, 64% of the patients had advanced to two or more injections of insulin a day, aiming for normal HbA1c. However, only a small additional fall in HbA1c was attained. Severe hypoglycemia was rare (two events per 100 patients per year) and not significantly different between the groups, nor were changes in weight, blood pressure, or plasma lipids. There were 61 new cardiovascular events in 40 patients and 10 deaths (6 due to cardiovascular causes).

CONCLUSIONS

Intense stepped insulin therapy in NIDDM patients who have failed glycemic control on pharmacological therapy is effective in maintaining near-normal glycemic control for > 2 years without excessive severe hypoglycemia, weight gain, hypertension, or dyslipidemia. Cardiovascular event rates are high at this stage of NIDDM. A long-term prospective trial is needed to assess the risk-benefit ratio of intensified treatment of hyperglycemia in NIDDM patients requiring insulin.
Serum Lipids and Lipoprotein(a) Concentrations in Chinese NIDDM Patients: Relation to metabolic control
Authors: Chang Chih-Jen , Kao Jau-Tsuen , Wu Ta-Jen , Lu Feng-Hwa , Tai Tong-Yuan
Published: March 2007

OBJECTIVE

To compare serum blood lipids and lipoprotein(a) [Lp(a)] levels in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients and nondiabetic control subjects and also to determine the influence of diabetes control on serum Lp(a) concentration in Chinese individuals.

RESEARCH DESIGN AND METHODS

We compared the serum blood lipids and Lp(a) levels in NIDDM patients (n = 100) and age- and sex-matched nondiabetic subjects (n = 100) who participated in a case-control study. Comparisons of Lp(a) concentrations were made between a normal control group, a group of diabetic patients with HbA1c < 8.0%, and a group of diabetic patients with HbA1c of 8% or higher.

RESULTS

The diabetic patients had higher total triglyceride, apolipoprotein B (apo B), and apo B-to-apo AI ratios, but lower high-density lipoprotein (HDL) cholesterol and apo AI concentrations than nondiabetic controls (P < 0.001, P < 0.01, P < 0.001, P < 0.05, and P < 0.001, respectively). A similar pattern of distribution of Lp(a) levels according to the degree of metabolic control was seen in patients with NIDDM and nondiabetic controls. No correlation was observed between Lp(a) levels and total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, apo AI, apo B, and triglyceride levels in all diabetic patients. No difference in the Lp(a) levels was noted between diabetic patients and nondiabetic subjects, even in poorly controlled diabetic patients.

CONCLUSIONS

In conclusion, Lp(a) levels are not elevated in diabetic patients, even in poorly controlled metabolic conditions.
Subcutaneous Glucose Concentration in Humans: Real estimation and continuous monitoring
Authors: Sternberg Fabio , Meyerhoff Carsten , Mennel Franz J , Bischof Friederike , Pfeiffer Ernst F
Published: March 2007

OBJECTIVE

To determine the real subcutaneous glucose concentration in healthy volunteers to help in the development of new calibration methods for subcutaneous glucosensors.

RESEARCH DESIGN AND METHODS

We developed a new method to estimate the real subcutaneous glucose concentration based on the recirculation of phosphate-buffered saline (PBS) in a microdialysis probe inserted into the subcutaneous tissue. Tissue glucose diffuses into the probe until complete equilibration between the glucose concentration outside and inside the microdialysis probe is achieved. Later, the glucose content of the recirculated PBS is assessed in vitro. We applied the method in 10 healthy volunteers under fasting state and during a hyperglycemic clamp. In addition, we monitored the subcutaneous glucose with an enzymatic-amperometric glucosensor combined with a microdialysis probe.

RESULTS

The subcutaneous glucose concentration measured by the recirculation method was 72 ± 6 and 78 ± 6% of the blood glucose measured in the fasting state and during the hyperglycemic clamps, respectively. On the other hand, the glucosensor's signal correlated significantly with the blood glucose.

CONCLUSION

The recirculation method estimated the real subcutaneous glucose concentration, opening the way to develop new calibration procedures for subcutaneous glucosensors. However, a suitable calibration procedure is still lacking.
Glucose Tolerance and Physical Activity in a Mexican Indigenous Population
Authors: Schulz Lesile O , Weidensee Richard C
Published: March 2007

OBJECTIVE

To assess diabetes prevalence and physical activity among an indigenous population in Mexico.

RESEARCH DESIGN AND METHODS

A total of 101 adult (mean age = 38 years) Mixtec Indians living on the outskirts of Huajuapan de Leon, Oaxaca, Mexico, volunteered to be measured for height, weight, blood pressure, glucose tolerance, and physical activity.

RESULTS

According to World Health Organization criteria, 2 women were diabetic and 42 subjects (15 men, 27 women) had impaired glucose tolerance (IGT). Although the population was generally lean, with a mean ± SD body mass index (BMI) of 23.0 ± 2.7 kg/m2 for men (n = 47) and 22.8 ± 3.0 kg/m2 for women (n = 54), the group with normal glucose tolerance had a significantly lower BMI than those with abnormal glucose tolerance (IGT or diabetes). Men were significantly more physically active than women, and a larger percentage of women (54%) than men (32%) had abnormal glucose tolerance. However, within gender groups, there was not a significant effect of physical activity on status of glucose tolerance.

CONCLUSIONS

The Mixtec population may be genetically predisposed to non-insulin-dependent diabetes, although their current lifestyle provides a protective effect. Less of a protective effect is seen for females, however. It is expected that further environmental changes impacting energy balance will have the most damaging repercussions for diabetes prevalence among Mixtec women.
Abnormalities of Antroduodenal Motility in Type I Diabetes
Authors: Samsom Melvin , Jebbink Rik J A , Akkermans Louis M A , Van Berge-Henegouwen Gerard P , Smout Andre J P M
Published: March 2007

OBJECTIVE

In the present study, a recently developed manometric technique was used to study antroduodenal motility in ambulant type I diabetic subjects.

RESEARCH DESIGN AND METHODS

In 12 patients with type I diabetes, antroduodenal manometry was performed for 20 h during the fasting period and the postprandial period after a standardized dinner and breakfast. All patients had evidence of cardiac autonomic neuropathy and complained of dyspeptic symptoms. During the manometric study, the blood glucose levels were frequently monitored and kept close to euglycemia in the diabetic patients. The results were compared with 12 healthy control subjects.

RESULTS

The migrating motor complex cycles observed in the diabetic subjects were longer than in the control subjects, 118.9 ± 46.0 vs. 87.0 ± 21.6 min (P < 0.05). This increase was attributable to a prolonged phase II, 78.0 ± 35.5 vs. 37.7 ± 18.5 min (P < 0.05). In the diabetic subjects, antral phase III was seen significantly < in the control subjects, 16.7 vs. 43.3% (P < 0.005). In 50% of the diabetic patients, total absence of antral phase III was observed-this phenomenon was not seen in the healthy control subjects. After dinner, the antral motility index was less in diabetic subjects compared with the healthy volunteers, indicating antral hypomotility (P < 0.01). Six diabetic patients showed abnormal duodenal activity such as early recurrence of phase III and bursts after dinner. No significant differences in antral motility index or in duodenal motility patterns were observed after breakfast. Six diabetic patients complained of dyspeptic symptoms after dinner, whereas none had dyspeptic symptoms after breakfast. In 67% of the patients, nausea was reported after an early phase III or a burst.

CONCLUSIONS

This study shows that prolonged ambulatory antroduodenal manometry is a feasible technique in patients. Recording multiple migrating motor complexes showed that interdigestive motor abnormalities of the stomach and duodenum are common in diabetic patients. Furthermore, it shows the occurrence of antral hypomotility and abnormal duodenal motility patterns after a high-calorie meal, with dyspeptic symptoms in diabetic patients being related to the composition of the meal.
Prevalence and Risk Factors for Micro- and Macroalbuminuria in an Italian Population-Based Cohort of NIDDM Subjects
Authors: Bruno Graziella , Cavallo-Perin Paolo , Bargero Giuseppe , Borra Milena , Calvi Valentina , D'Errico Nicola , Deambrogio Piercarlo , Pagano Gianfranco
Published: March 2007

OBJECTIVE

To determine the prevalence of micro- and macroalbuminuria in NIDDM and their relationship with some known and putative risk factors.

RESEARCH DESIGN AND METHODS

Out of a population-based cohort of 1,967 NIDDM subjects, 1,574 were investigated (80%). Albumin excretion rate (AER) was evaluated on an overnight urine collection, and plasma and urine determinations were centralized.

RESULTS

The prevalences of microalbuminuria (AER 20–200 μg/min), macroalbuminuria (AER > 200 μg/min), and hypertension were 32.1% (95% CI 29.8–34.4), 17.6% (15.7–19.5), and 67% (64.6–69.3), respectively. Apart from prevalence of hypertension, which after adjustment for age, BMI, and duration of diabetes was 2.3 times higher in women, rates were higher in men (odds ratio [OR] 1.31, 95% CI 1.04–1.66 for microalbuminuria and OR 1.63, 1.22–2.17 for macroalbuminuria). In comparison with normoalbuminuric subjects, both micro- and macroalbuminuric diabetic subjects had significantly longer duration of diabetes, higher levels of systolic blood pressure, fasting plasma glucose, HbA1c, triglycerides, and uric acid; in macroalbuminuric subjects only, levels of apolipoprotein B and HDL cholesterol were, respectively, higher and lower than in normo- and microalbuminuric subjects. In logistic regression, variables independently related to both micro- and macroalbuminuria were age, HbA1c, cigarette smoking habits, plasma uric acid, and diastolic blood pressure, after adjustment for plasma creatinine and diabetic treatment. In addition, duration of diabetes and HDL cholesterol levels were associated with macroalbuminuria.

CONCLUSIONS

This population-based study showed high prevalence of micro- and macroalbuminuria in NIDDM subjects, who were characterized by a more adverse pattern of cardiovascular risk factors.
Age-Related Alteration of Pancreatic β-cell Function: Increased proinsulin and proinsulin-to-insulin molar ratio in elderly, but not in obese, subjects without glucose intolerance
Authors: Shimizu M , Kawazu S , Tomono S , Ohno T , Utsugi T , Kato N , Ishii C , Ito Y , Murata K
Published: March 2007

OBJECTIVE

To determine the secretion of insulin, C-peptide, and proinsulin after oral glucose loading in healthy elderly subjects compared with middle-aged subjects with and without obesity and with NIDDM.

RESEARCH DESIGN AND METHODS

Subjects fell into four groups: nonobese middle-aged normal control subjects (CNT group; n = 38, 40–64 years old); obese normal subjects (OB group; n = 18, 40–64 years old); nonobese NIDDM subjects (NIDDM group; n = 28, 40–64 years old); and nonobese elderly subjects (OL group; n = 17, 65–92 years old). Insulin, C-peptide, and proinsulin were determined by radioimmunoassay in plasma samples taken at 0, 30, 60, and 120 min during a 75-g oral glucose tolerance test (OGTT).

RESULTS

There were no differences in plasma glucose during the OGTT among the three nondiabetic groups. Hyperinsulinemia was significant in the OB and NIDDM groups but not in the OL group. On the other hand, absolute hyperproinsulinemia was significant in the OL and NIDDM groups compared with the CNT group. Increased proinsulin was rather dominant in the OL group, especially late after glucose loading. Molar ratios of proinsulin to insulin or C-peptide thus were significantly higher in the OL and NIDDM groups.

CONCLUSIONS

Alteration of pancreatic β-cell function independent of that seen with NIDDM occurred in relation to aging. This may be a predisposing factor to the development of impaired glucose tolerance or NIDDM in elderly subjects, that is, independent of obesity.
Sex Hormones and DHEA-SO4 in Relation to Ischemic Heart Disease Mortality in Diabetic subjects: The Wisconsin Epidemiologic Study of Diabetic Retinopathy
Authors: Haffner Steven M , Moss Scot E , Klein Barbara EK , Klein Ronald
Published: March 2007

OBJECTIVE

Sex hormones are associated with atherogenic changes in lipoproteins and changes in glucose and insulin metabolism, yet few data are available on the relationship of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to ischemic heart disease (IHD) in diabetic subjects, a groupwith very high levels of IHD.

RESEARCH DESIGN AND METHODS

We examined the relation of total and free testosterone, sex hormone binding globulin, estrone, estradiol, and DHEA-SO4 to the 5-year IHD mortality in the older-onset diabetic subjects in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) in a matched diabetic subject-control design (two control subjects for every diabetic subject).

RESULTS

In men (n = 123), none of the sex hormones or DHEA-SO4 significantly predicted IHD mortality. In women (n = 120), lower levels of DHEA-SO4 (P < 0.01) and total testosterone (P = 0.07) predicted IHD mortality. These results were essentially unchanged after adjustment for duration of diabetes, GHb, diuretic use, and serum creatinine, which are major predictors of IHD mortality in the WESDR. Finding lower testosterone levels in diabetic subjects of IHD in women is contrary to data on risk factors, which suggests that increased androgen activity may beassociated with worse IHD risk factors.

CONCLUSIONS

This study suggests that alterations in sex hormones and DHEA-SO4 are unlikely to explain a major proportion of the variation in IHD mortality in diabetic subjects.
Demonstration of Regional Sympathetic Denervation of the Heart in Diabetes: Comparison between patients with NIDDM and IDDM
Authors: Turpeinen Anu K , Vanninen Esko , Kuikka Jyrki T , Uusitupa Matti IJ
Published: March 2007

OBJECTIVE

Global myocardial uptake of 123I-metaiodobenzylguanidine (MIBG) has been shown to be decreased in diabetic patients with autonomic neuropathy, indicating cardiac sympathetic dysfunction. However, possible differences in myocardial MIBG distribution between NIDDM and IDDM diabetic patients are not known.

RESEARCH DESIGN AND METHODS

Regional myocardial distribution of 123I-MIBG was studied in seven male IDDM patients (age 45 ± 2 years, duration of diabetes 30 ± 3 years, means ± SE) and 13 NIDDM patients (8 men, 5 women, age 59 ± 2 years, duration of diabetes 10 ± 1 years). A dual-tracer single-photon emission tomography was carried out with 123I-MIBG and 99mTc-methoxyisobutylisonitrrile to asses simultaneously myocardial sympathetic innervation and perfusion at rest. Conventional autonomic nervous function tests, power spectral analysis of heart rate variability, and echocardiography were performed for assessments of autonomic function and cardiac dimensions and function.

RESULTS

Autonomic nervous function tests and echocardiography showed similar results in IDDM and NIDDM patients. Despite this, global myocardial MIBG uptake (0.43 ± 0.04 vs. 0.59 ± 0.06, P = 0.03) and MIBG heart-to-liver ratio (0.59 ± 0.03 vs. 0.68 = 0.03, P = 0.05) were lower in NIDDM compared with IDDM patients. Regional distribution of MIBG uptake and regional MIBG/perfusion ratio revealed significantly reduced uptake in NIDDM patients especially in the inferoposterior segments of the left ventricle compared with IDDM patients. Difference in age between NIDDM and IDDM patients did not explain the results.

CONCLUSIONS

Reduced myocardial MIBG uptake was found in NIDDM patients compared withthe uptake in IDDM patients, particularly involving inferoposterior segments.Regional sympathetic damage not detectable with conventional autonomic function tests is relatively common in NIDDM.
Differing Effects of Pancreas-kidney Transplantation With Systemic Versus Portal Venous Drainage on Cholesteryl Ester Transfer in IDDM Subjects
Authors: Bagdade John D , Ritter Mary C , Kitabchi Abbas E , Huss Emer , Thistlethwaite Richard , Gaber Osama , Lambeth Helen
Published: March 2007

OBJECTIVE

Cholesteryl ester transfer (CET) is accelerated in patients with IDDM treated with conventional (subcutaneous) insulin therapy (CIT) and a number of other disorders associated with premature cardiovascular disease. We have shown that in IDDM this disturbance is closely linked to iatrogenic hyperinsulinemia (HI), because it was reversed when insulin was administered by the intraportal (IP) route. In this study, we sought to determine whether HI after successful pancreas-kidney transplantation (PKT) has the same adverse effect on CET.

RESEARCH DESIGN AND METHODS

CET was measured by both mass and isotopic assays and compared in two groups of euglycemic non-insulin-requiring IDDM PKT patients with either systemically draining allografts and persistent HI or grafts with portal vein anastomoses that were normoinsulinemic (PK-P). A third group of eight nondiabetic kidney transplant (KT) patients receiving the same immunosuppressive drugs served as control subjects.

RESULTS

CET in pancreas-kidney transplantation subjects with systemic venous drainage (PK-S) was increased (P < 0.001) to the same level we have reported previously in IDDM patients receiving CIT and was significantly higher (P < 0.001) than in those subjects with PK-P. CET in the PK-P group did not differ from that of the KT control patients.

CONCLUSIONS

CET is affected by variations in systemic insulin levels in pancreas transplant patients with allografts that have differing venous drainage. Because high systemic insulin levels are linked to the activation of (ET, euglycemic HI IDDM pancreas allograft recipients may continue to be at high risk for macrovascular complications.
A Prospective Analysis of the HOMA Model: The Mexico City Diabetes Study
Authors: Haffner Steven M , Gonzalez Clicerio , Miettinen Heikki , Kennedy Esmarie , Stern Michael P
Published: March 2007

OBJECTIVE

Both insulin resistance (IR) and decreased insulin secretion have been shown to predict the development of NIDDM. However, methods to assess insulin sensitivity and secretion are complicated and expensive to apply in epidemiological studies. The homeostasis model assessment (HOMA) has been suggested as a method to assess IR and secretion from the fasting glucose and insulin concentrations.

RESEARCH DESIGN AND METHODS

We applied the HOMA model in the 3.5-year follow-up of the Mexico City Diabetes Study.

RESULTS

Out of 1,449 subjects, 97 developed diabetes. When modeled separately insulin resistance but not insulin secretion predicted NIDDM. However, when both variables were entered into the same regression model, both increased IR and decreased β-cell function significantly predicted NIDDM.

CONCLUSIONS

We conclude that the HOMA provides a useful model to assess ²-cell function in epidemiological studies and that it is important to take into account the degree of IR in assessing insulin secretion.
Metformin's Effects on Glucose and Lipid Metabolism in Patients with Secondary Failure to Sulfonylureas
Authors: Fanghänel Guillermo , Sánchez-Reyes Leticia , Trujillo Cesar , Sotres David , Espinosa-Campos Jorge
Published: March 2007

OBJECTIVE

To compare results obtained with metformin versus those obtained with DNA-recombinant insulin in obese patients with NIDDM suffering from secondary failure to sulfonylureas.

RESEARCH DESIGN AND METHODS

We conducted an open, prospective, randomized, and comparative study comprising a total of 60 patients selected and placed in two parallel groups. We had previously confirmed that the subjects had secondary failure to high doses of sulfonylureas. The initial metformin dosage was a single 850 mg tablet, and the dosage was increased to two or three tablets depending on the patient's metabolic changes. The initial dosage of DNA-recombinant insulin was 24 U, subcutaneously administered and divided into two portions: two-thirds at around 8:00 A.M., before breakfast, and the remaining third at 8:00 P.M., before dinner. The dosage was adjusted based on the patient's clinical and metabolic response.

RESULTS

The initial average glucose value for the metformin group was 269.1 ± 32.2 mg/dl, decreasing by the end of the study to 159.7 ± 30.5 mg/dl. For the insulin group, these figures went from 270.7 ± 24.0 mg/dl at the beginning of the study to 134.8 ± 26.7 mg/dl. This decrease correlates with the reduction in glycosylated hemoglobin from 12.8 to 8.9% for the first group and from 12.3 to 8.2% for the second, as well as with the reduction in triglyceride values from 230.3 to 183.1 mg/dl and from 218.4 to 186.3 mg/dl, respectively. The BMI (27.5–26.4), blood pressure (systolic from 145.7–132.1 mmHg, diastolic from 90.3–84.8 mmHg), and total cholesterol levels (235–202 mg/dl) decreased in only the metformin group.

CONCLUSIONS

Metformin is an effective, safe, and well-tolerated treatment that improves metabolic control and favorably modifies secondary clinical alterations due to insulin resistance, such as arterial hypertension, overweight, and hyperlipidemia, in obese patients with NIDDM suffering from secondary failure to sulfonylureas.
Long-Term Effects of Fish Oil on Insulin Resistance and Plasma Lipoproteins in NIDDM Patients With Hypertriglyceridemia
Authors: Rivellese Angela A , Maffettone Ada , Iovine Ciro , Di Marino Lucrezia , Annuzzi Giovanni , Mancini Mario , Riccardi Gabriele
Published: March 2007

OBJECTIVE

The aim of this study was to evaluate the long-term (6-month) effects of moderate fish oil supplementation on insulin sensitivity and plasma lipoproteins in NIDDM patients with hypertriglyceridemia.

RESEARCH DESIGN AND METHODS

The study has been performed according to a randomized double-blind placebo-controlled design with a parallel group sequence. After a washout period of 4 weeks and a run-in period of 3 weeks, 16 NIDDM patients with hypertriglyceridemia (triglyceride [TG], 2.25–5.65 mmol/l) were randomly assigned to either fish oil (2.7 g/day eicosapentaenoic plus docosahexaenoic acid for 2 months, then 1.7 g/day for 4 more months) (n = 8) or placebo (n = 8). Diet and hypoglycemic drugs remained unchanged throughout the whole experiment. At baseline and after 6 months, insulin sensitivity was measured by euglycemic hyperinsulinemic clamp (insulin infused, 2.0 mIU · kg−1 body wt · min−1). At the same time, blood glucose control, fasting and postprandial serum insulin and nonesterified fatty acid (NEFA) concentrations, and fasting plasma lipoprotein concentrations were evaluated.

RESULTS

In the group treated with ffish oil compared with the baseline, there was: 1) a significant reduction in both plasma TG (2.92 ± 0.23 vs. 3.85 ± 0.32 [mean ± SE] mmol/l, P < 0.001) and VLDL-TG (2.35 ± 0.24 vs. 4.25 ± 0.66 mmol/l, P < 0.01), without significant changes in blood glucose control; 2) a significant reduction in fasting NEFA concentrations (572 ± 100 vs. 825 ± 131 μmol/l, P < 0.01); and 3) a significant enrichment in long-chain ω-3 fatty acids of erythrocyte membrane phospholipids. In the placebo group, there were no changes in any of the variables analyzed. The insulin-mediated glucose uptake was unchanged in both groups (fish oil, 4.04 ± 0.82 mg · kg−1 · min−1 at baseline and 3.96 ± 0.50 mg · kg−1 · min−1 at 6 months; placebo, 3.51 ± 0.62 mg · kg−1 · min−1 at baseline and 4.09 ± 0.49 mg · kg−1 · min−1 at 6 months).

CONCLUSIONS

In NIDDM patients with hypertriglyceridemia, moderate amounts of fish oil induce a long-term significant reduction in plasma triglycerides, VLDL triglycerides, and NEFA and a significant enrichment in the erythrocyte phospholipid content of long-chain ω-3 fatty acids, without deteriorating blood glucose control. However, this amount of ω-3 fatty acids was unable to improve insulin sensitivity in this group of patients.