bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of the Trp64Arg polymorphism of the beta3-adrenergic receptor in Greek women with gestational diabetes.
Authors: Alevizaki M , Thalassinou L , Grigorakis S I , Philippou G , Lili K , Souvatzoglou A , Anastasiou E
Published: March 2007

OBJECTIVE: This study assessed whether the Trp(64)Arg polymorphism of the beta3-adrenergic receptor (beta3-AR), which has been associated with obesity, insulin resistance, weight gain, and earlier onset of type 2 diabetes, is more frequent in women who develop gestational diabetes mellitus (GDM) or whether it is associated with weight gain during pregnancy RESEARCH DESIGN AND METHODS: A total of 311 Greek pregnant women (180 with GDM and 131 without GDM [control]) who underwent a 100-g oral glucose tolerance test (OGTT) in the third trimester of pregnancy were genotyped for the beta3-AR Arg(64) polymorphism. Insulin levels were also determined during the OGTT. RESULTS: The frequency of Trp(64)Arg heterozygotes in this population was approximately 7% and was similar in the GDM and control groups (6.7 vs. 6.9%) as well as in the obese (BMI > or =27 kg/m2) and the nonobese (6.3 vs. 6.8%) subgroups. In the GDM group, BMI, fasting insulin resistance index, and diastolic blood pressure were significantly higher in Trp(64)Arg carriers; these differences were no longer observed when obesity was considered. In the 4 subgroups (control Trp(64)Trp and Trp(64)Arg and GDM Trp(64)Trp and Trp(64)Arg), a highly significant trend was evident of an increase in the percentage of subjects with shorter height. CONCLUSIONS: The frequency of the Arg(64) allele in Greek pregnant women is relatively rare compared with other ethnic groups and is probably not related to the development of GDM or obesity The observed tendency for shorter body height in Arg(64) carriers merits further evaluation in larger population samples.
A new consensus error grid to evaluate the clinical significance of inaccuracies in the measurement of blood glucose.
Authors: Parkes J L , Slatin S L , Pardo S , Ginsberg B H
Published: March 2007

OBJECTIVE: The objectives of this study were 1) to construct new error grids (EGs) for blood glucose (BG) self-monitoring by using the expertise of a large panel of clinicians and 2) to use the new EGs to evaluate the accuracy of BG measurements made by patients. RESEARCH DESIGN AND METHODS: To construct new EGs for type 1 and type 2 diabetic patients, a total of 100 experts of diabetes were asked to assign any error in BG measurement to 1 of 5 risk categories. We used these EGs to evaluate the accuracy of self-monitoring of blood glucose (SMBG) levels in 152 diabetic patients. The SMBG data were used to compare the new type 1 diabetes EG with a traditional EG. RESULTS: Both the type 1 and type 2 diabetes EGs divide the risk plane into 8 concentric zones with no discontinuities. The new EGs are similar to each other, but they differ from the traditional EG in several significant ways. When used to evaluate a data set of measurements made by a sample of patients experienced in SMBG, the new type 1 diabetes EG rated 98.6% of their measurements as clinically acceptable, compared with 95% for the traditional EG. CONCLUSIONS: The consensus EGs furnish a new tool for evaluating errors in the measurement of BG for patients with type 1 and type 2 diabetes.
Soluble transferrin receptor level: a new marker of iron deficiency anemia, a common manifestation of gastric autoimmunity in type 1 diabetes.
Authors: De Block C E , Van Campenhout C M , De Leeuw I H , Keenoy B M , Martin M , Van Hoof V , Van Gaal L F
Published: March 2007

OBJECTIVE: A total of 15-20% of type 1 diabetic patients have parietal cell antibodies (PCAs). PCA+ subjects are at increased risk for iron deficiency anemia and atrophic gastritis. Recently, soluble transferrin receptor (sTfR) levels have proven to be a sensitive indicator for iron deficiency They are, in contrast with ferritin levels, independent of inflammation, liver and hormonal status, and sex. We are the first to evaluate sTfR levels in type 1 diabetes and tested the hypothesis of higher sTfR levels in patients with PCAs and/or autoimmune gastritis. RESEARCH DESIGN AND METHODS: We examined 148 type 1 diabetic patients (85 men and 63 women; 50 were PCA+) and 59 sex- and age-matched control subjects (30 men and 29 women). The main outcome measures were sTfR levels, iron deficiency anemia, and atrophic gastritis. Logistical regression analysis tested risk factors for iron deficiency RESULTS: Iron deficiency was present in 38 subjects. Iron (P<0.0001) and ferritin (P<0.0001) levels but not sTfR levels were lower in women. sTfR levels were similar in diabetic and control subjects but were higher in PCA+ subjects (P = 0.015). In diabetic subjects, iron deficiency anemia was more prevalent in PCA+ than in PCA- patients (odds ratio 3.07, P = 0.013) and was associated with sex (P = 0.0001), age (P = 0.046), and sTfR (P = 0.0008) levels. Atrophic gastritis was present in 15 of 28 PCA+ and in 1 of 11 PCA diabetic subjects (P = 0.014). sTfR levels tended to be higher in patients with atrophic gastritis (P = 0.062). CONCLUSIONS: In type 1 diabetes, sTfR levels can be used to diagnose iron deficiency anemia, which is more prevalent in PCA+ subjects. sTfR levels are higher in PCA+ individuals who are at risk for developing atrophic gastritis.
Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes.
Authors: Teno S , Uto Y , Nagashima H , Endoh Y , Iwamoto Y , Omori Y , Takizawa T
Published: March 2007

OBJECTIVE: Serum triglyceride levels are important in the development of atherosclerosis. Although triglyceride levels are generally increased in the postprandial periods, the association between postprandial triglyceride (pTG) levels and atherosclerosis has not been investigated in diabetic patients. To investigate the role of pTG levels in atherosclerosis, we examined the correlation between pTG levels and carotid intimal-medial thickness (IMT). RESEARCH DESIGN AND METHODS: Carotid IMT was measured by ultrasonography in 61 patients with type 2 diabetes. Plasma glucose (PG), insulin, total cholesterol, triglycerides, and HDL cholesterol levels were measured after overnight fasting and 4 h after a meal. RESULTS: Carotid IMT of the patients with fasting hypertriglyceridemia was greater than that of the patients with normal fasting triglyceride (fTG) levels (0.85+/-0.12 vs. 0.76+/-0.14 mm; P = 0.02). The carotid IMT was increased in the patients with pTG levels >2.27 mmol/l. The normo-normo (NN) and normo-hyper (NH) groups consisted of patients with normal fTG levels but with pTG levels <2.27 and >2.27 mmol/l, respectively. Patients with both hypertriglyceridemia and pTG levels >2.27 mmol/l formed the hyper-hyper (HH) group. Carotid IMT was significantly increased in the NH (0.86+/-0.13 mm) and HH (0.85+/-0.12 mm) groups compared with the NN group (0.73+/-0.13 mm; P<0.01). Although postprandial PG, pTG, and fasting LDL cholesterol levels were all independently correlated with carotid IMT, pTG levels had the strongest statistical influence (P = 0.002). CONCLUSIONS: Postprandial hypertriglyceridemia despite normal fTG levels may be an independent risk factor for early atherosclerosis in type 2 diabetes.
Involvement of Peripheral Polymorphonuclear Leukocytes in Oxidative Stress and Inflammation in Type 2 Diabetic Patients
Authors: Shurtz-Swirski Revital , Sela Shifra , Herskovits Avraham T. , Shasha Shaul M. , Shapiro Galina , Nasser Lubna , Kristal Batya
Published: March 2007

OBJECTIVE— To determine the extent to which peripheral polymorphonuclear leukocytes (PMNs) contributed to oxidative stress (OS) and inflammation in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS— PMNs and plasma were separated from blood withdrawn from 18 type 2 diabetic patients and 16 age- and sex-matched normal control subjects. The rate of superoxide release from phorbol 12-myristate 13-acetate (PMA)-stimulated PMNs and the plasma glutathione (GSH) levels served as measures of OS. Inflammation was assessed by PMN recruitment, expressed by peripheral blood PMN counts, and the in vitro survival of PMNs, which reflects cell necrosis.

RESULTS— PMA-stimulated PMNs from diabetes released superoxide significantly faster, and plasma-reduced GSH was lower in diabetic patients than in normal control subjects. The rate of superoxide release from diabetic PMNs showed no correlation with the plasma glucose concentrations, whereas a positive linear correlation with HbAlc was found. The in vitro survival of diabetic PMNs was lower than normal control PMNs when each was incubated in its own serum. The in vitro survival of normal control PMNs was reduced when incubated with diabetic serum, whereas normal control sera promoted the survival of diabetic PMNs. Peripheral PMN counts were higher in diabetic patients than in normal control patients.

CONCLUSIONS— Type 2 diabetes is accompanied by a priming of PMNs, resulting in OS and increased self-necrosis. Necrosis starts a chain of inflammatory reactions that result in cell recruitment and in the long run,with OS, may result in endothelial dysfunction. Understanding the contribution of PMNs to OS and inflammation in diabetes may illuminate new mechanisms through which endothelial dysfunction evolves and causes angiopathy and atherosclerosis.
Early Detection of Microcirculatory Impairment in Diabetic Patients With Foot at Risk
Authors: Zimny Stefan , Dessel Frauke , Ehren Marianne , Pfohl Martin , Schatz Helmut
Published: March 2007

OBJECTIVE—To assess microcirculatory impairment and alterations of the skin oxygen supply in diabetic patients with foot at risk.

RESEARCH DESIGN AND METHODS—This study evaluated skin blood flow in 21 type 2 diabetic patients with a foot at risk (defined as a foot with neuropathy but without ulceration or previous ulcerations), 20 type 2 diabetic patients without foot lesions or neuropathy, and 21 normal subjects as a control group. The skin blood flow was determined by measuring the transcutaneous oxygen pressure (TcPo2) at the dorsum of the foot in supine and sitting position. The clinical assessment included standard measures of peripheral and autonomic neuropathy, but peripheral vascular disease was excluded by Doppler ultrasound.

RESULTS—In supine position, TcPo2 was significantly reduced (means ± SE) in diabetic patients with foot at risk (6.04 ± 0.52 kPa) compared with diabetic (7.14 ± 0.43 kPa, P = 0.035) and nondiabetic (8.10 ± 0.44 kPa, P = 0.01) control subjects. The sitting/supine TcPo2 difference was higher in diabetic subjects with foot at risk (3.13 ± 0.27 kPa) compared with both diabetic (2.00 ± 0.18, P = 0.004) and nondiabetic (1.77 ± 0.15 kPa, P = 0.0003) control subjects. The mean sitting/supine ratio was 1.70 ± 0.12 in diabetic patients with foot at risk, 1.32 ± 0.04 in diabetic control subjects, and 1.25 ± 0.03 in nondiabetic control subjects (P = 0.007). The sitting/supine TcPo2 ratio was negatively correlated with the heart rate variation coefficient at rest (r = −0.32, P = 0.044) and at deep respiration (r = −0.31, P = 0.046).

CONCLUSIONS—Our data indicate that skin oxygen supply is reduced in type 2 diabetic patients with foot at risk. This is probably due to an impaired neurogenic blood flow regulation and may contribute to capillary hypertension, followed by disturbed endothelial function leading to edema and skin damage of the foot. The determination of TcPo2 appears to be a useful tool in screening type 2 diabetic patients for foot at risk.
Insulin Resistance After Renal Transplantation
Authors: Hjelmesæth Jøran , Midtvedt Karsten , Jenssen Trond , Hartmann Anders
Published: March 2007

OBJECTIVE—The purpose of the present study was to validate various surrogate estimates of insulin sensitivity (IS) in a renal transplant population and to assess the influence of immunosuppressive and antihypertensive therapy on insulin resistance (IR) after renal transplantation.

RESEARCH DESIGN AND METHODS—A total of 167 consecutive renal transplant recipients without previously known diabetes underwent a 75-g oral glucose tolerance test (OGTT) 3 months after renal transplantation. A total of 43 patients also underwent a euglycemic-hyperinsulinemic glucose clamp study. Six OGTT-derived IS indexes were validated against the euglycemic-hyperinsulinemic glucose clamp–derived IS index (ISICLAMP).

RESULTS—The OGTT-derived ISITX correlated closely with the ISICLAMP (r = 0.58, P < 0.001). The other surrogate estimates of IS were also significantly but less well correlated with the ISICLAMP (Spearman’s correlation; r = −0.45 to 0.41, P = 0.003–0.050). In the univariate model, BMI, daily prednisolone dose, creatinine clearance, hypertension, number of antihypertensive agents, and use of diuretics or β-blockers were negatively associated with ISITX (P < 0.05). After multiple regression analysis, BMI (P < 0.001), daily prednisolone dose (P < 0.001), cytomegalovirus infection (P = 0.030), and triglycerides (P = 0.034) were shown to be independent predictors of posttransplant IR.

CONCLUSIONS—The OGTT-derived ISITX may be a useful estimate of IS in Caucasian renal transplant recipients. Increasing daily prednisolone dose is an independent predictor of IR after renal transplantation. Hypertension and the use of β-blockers and diuretics may also deteriorate IR in this group of patients.
Simple Screening Tests for Peripheral Neuropathy in the Diabetes Clinic
Authors: Perkins Bruce A. , Olaleye David , Zinman Bernard , Bril Vera
Published: March 2007

OBJECTIVE— The utility of rapid and reliable sensory tests appropriate for the diagnosis of neuropathy in the diabetes clinic, rather than as prognostic tools for the prediction of foot complications, has been unclear because of limitations inherent in previous studies. Although clinical practice guidelines recommend annual screening for neuropathy, they are unable to support specific recommendations for screening maneuvers because of a lack of evidence for the validity of screening tests in the medical literature. The objective of this study was to assess the operating characteristics of four simple sensory screening maneuvers as compared with standardized electrophysiological tests in the diagnosis of distal symmetrical polyneuropathy.

RESEARCH DESIGN AND METHODS— We assessed four simple tests(the 10-g Semmes-Weinstein monofilament examination [SWME], superficial pain sensation, vibration testing by the on-off method, and vibration testing by the timed method) in 478 subjects with independent blinded evaluations compared against the criterion standard of nerve conduction studies. We present receiver-operating characteristic (ROC) curves, positive and negative likelihood ratios, and sensitivity and specificity values for each test.

RESULTS— The four simple screening maneuvers reveal similar operating characteristics. Cutoff points by ROC curve analyses reveal that a positive or abnormal test is represented by five incorrect responses of eight stimuli applied. A negative or normal test is represented by one or fewer incorrect responses of eight stimuli applied. By these criteria, the point estimates of the positive likelihood ratios for vibration testing by the on-off method, vibration testing by the timed method, the SWME, and superficial pain sensation test are 26.6, 18.5, 10.2, and 9.2, respectively. The point estimates of the negative likelihood ratios are 0.33, 0.51, 0.34,and 0.50, respectively. The screening tests showed comparable sensitivity and specificity results. The 10-g SWME, superficial pain test, and vibration testing by the on-off method are rapid, each requiring ∼60 s to administer. The timed vibration test takes longer, and the interpretation is more complicated. The combination of two simple tests (e.g., the 10-g SWME and vibration testing by the on-off method) does not add value to each individual screening test.

CONCLUSIONS— Annual screening for diabetic neuropathy should be conducted using superficial pain sensation testing, SWME, or vibration testing by the on-off method. The reported operating characteristics for each sensory modality can be applied to positive findings on the physical examination of individual patients to predict the likelihood of neuropathy.
The Impact of the Diabetes Control and Complications Trial and Humalog Insulin on Glycohemoglobin Levels and Severe Hypoglycemia in Type 1 Diabetes
Authors: Chase H. Peter , Lockspeiser Tai , Peery Ben , Shepherd Mark , MacKenzie Todd , Anderson James , Garg Satish K.
Published: March 2007

OBJECTIVE—This study was performed to determine the effects of the Diabetes Control and Complications Trial (DCCT) report in 1993 and the introduction of Lispro (Humalog) insulin in 1996 on glycemic control and on the number of severe hypoglycemic episodes in type 1 diabetic patients of various ages.

RESEARCH DESIGN AND METHODS—Diabetes care parameters and HbA1c data from 884 subjects with type 1 diabetes were entered into our database at the time of clinic visits from 1993 through 1998. In addition, a questionnaire was sent to all patients to validate the number of insulin injections per day, the incidence of severe hypoglycemic episodes (as defined by the DCCT), and the use of Humalog insulin. Data were divided into four age-groups: <5, 5–12, 13–18, and >18 years of age.

RESULTS—Longitudinal HbA1c levels declined significantly after the DCCT report in 1993–1996 (P < 0.001), but the number of severe hypoglycemic events increased (P < 0.001). A second decline in HbA1c levels was observed after the introduction of Humalog insulin in 1996 (P < 0.001). However, severe hypoglycemic episodes did not change (P = 0.26).

CONCLUSIONS—Administration of Humalog resulted in an additional reduction in HbA1c levels beyond the reduction in HbA1c values after the DCCT report. In contrast to the increase in severe hypoglycemic events after the DCCT results, the number of severe hypoglycemic episodes did not increase after the introduction of Humalog, despite a further decrease in HbA1c values.
Antiatherogenic Mitochondrial Genotype in Patients With Type 2 Diabetes
Authors: Matsunaga Hajime , Tanaka Yasushi , Tanaka Masashi , Gong Jian-Sheng , Zhang Jin , Nomiyama Takashi , Ogawa Osamu , Ogihara Takeshi , Yamada Yoshiji , Yagi Kunio , Kawamori Ryuzo
Published: March 2007

OBJECTIVE—To evaluate the significance of a longevity-associated mitochondrial genotype (Mt5178A) derived from a C → A transversion at nucleotide position 5178 of mitochondrial DNA, which causes a Leu-to-Met substitution within the NADH dehydrogenase subunit 2 gene, in type 2 diabetic subjects.

RESEARCH DESIGN AND METHODS—Mt5178 typing was done by polymerase chain reaction–restriction fragment-length polymorphism with the restriction enzyme AluI in 1,148 type 2 diabetic Japanese subjects, and the results were compared with the clinical characteristics. Then, the association of Mt5178 type with early atherosclerotic changes of the bilateral carotid arteries on ultrasonography was assessed in 412 diabetic subjects randomly selected from the original 1,148 type 2 diabetic subjects, while maintaining the same frequency of Mt5178A and Mt5178C.

RESULTS—The frequency of Mt5178A in the type 2 diabetic subjects (454 of 1,148; 40%) was not different from that previously found in healthy blood donors (114 of 252; 45%). Clinical characteristics regarding diabetes were not significantly different between the Mt5178A group (n = 454) and the Mt5178C group (n = 694). However, the mean intima-media thickness (IMT) at six sites in the bilateral carotid arteries was significantly smaller in the Mt5178A group than in the Mt5178C group (0.906 ± 0.018 vs. 0.995 ± 0.021 mm, mean ± SEM, P = 0.022), and the Mt5178 type was significantly correlated with both the mean IMT and the presence of plaque on multiple regression analysis and discriminant analysis.

CONCLUSIONS—The Mt5178A genotype may be unrelated to the etiology of type 2 diabetes. However, Mt5178A seems to have an antiatherogenic effect, at least in type 2 diabetic individuals.
Na/Li Countertransport Abnormalities in Type 1 Diabetes With and Without Nephropathy Are Familial
Authors: Mead Paul A. , Wilkinson Robert , Thomas Trevor H.
Published: March 2007

OBJECTIVE—To determine whether there is a familial abnormality in erythrocyte Na/Li countertransport (CT) kinetics in the approximate one-third of type 1 diabetic patients that succumb to a familial predisposition to nephropathy.

RESEARCH DESIGN AND METHODS—Erythrocyte Na/Li CT kinetics were measured in nondiabetic first-degree relatives of type 1 diabetic patients with nephropathy (DNrel) (n = 32) or without nephropathy (DCrel) (n = 22) and normal control subjects ( n = 25).

RESULTS—Increases in outside-site Na ion association rate constant and turnover rate of Na/Li countertransport (CT) in DNrels caused increases in Vmax/Km and Vmax, respectively. Thiol alkylation with N-ethylmaleimide (NEM) modifies these kinetic parameters abnormally in nephropathy. With Na ions at the outside site of the transporter, thiol alkylation causes a large decrease in Vmax; but in their absence, Vmax is decreased in normal control subjects, unchanged in DCrels, or increased in DNrels. The relationship between Vmax values after thiol alkylation with or without Na ions was different in DNrels (P < 0.001). Kinetic parameters with and without thiol alkylation identified 60% of DNrels and 20% of DCrels as abnormal. The single-flux rate assay of Na/Li CT did not give this discrimination, and its use may cause discrepancy between studies.

CONCLUSIONS—Clinically normal untreated DNrels have the same abnormality in Na/Li CT as the affected patients. DNrels had a metabolic syndrome with increased BMI and plasma triglycerides, but no elevation in blood pressure. Na/Li CT can detect those type 1 diabetic patients at risk of nephropathy who have a familial abnormality in a membrane thiol protein.
Epipen as an Alternative to Glucagon in the Treatment of Hypoglycemia in Children With Diabetes
Authors: Monsod Teresa P.C. , Tamborlane William V. , Coraluzzi Luisa , Bronson Mary , Yong-Zhan Ma Tony , Ahern Jo Ann
Published: March 2007

OBJECTIVE—Fear of a severe hypoglycemic reaction is a major obstacle to achieving near-normal plasma glucose levels. Although parenteral glucagon is effective in treating these reactions, it is cumbersome to use, causes severe nausea, and is impractical in the school setting. Epinephrine is available as a premixed injection (Epipen) that may be used by all care providers. Using Epipen to treat hypoglycemia may be an effective, safe, and easy-to-use alternative to glucagon.

RESEARCH DESIGN AND METHODS—Ten children (age 11.7 ± 2.4 years) with type 1 diabetes were studied on two occasions. After an overnight equilibration period, hypoglycemia was induced via an insulin pump (1 mU · kg–1 · min–1). At a blood glucose level of 2.8 mmol/l, either glucagon (1 mg) or epinephrine (0.3 mg), in random order, was administered intramuscularly and responses were monitored.

RESULTS—Plasma free insulin concentrations were similar in both studies. Plasma glucose levels increased by 1.7 ± 0.2 mmol/l (mean ± SEM) in 10 min and by 2.6 ± 0.2 mmol/l in 15 min with administration of glucagon and were not consistently increased with administration of epinephrine (P < 0.01). Peak glucagon concentrations after administration of glucagon were >60-fold higher than basal concentrations. After administration of epinephrine, peak epinephrine levels were 20-fold higher than basal concentrations.

CONCLUSIONS—Epinephrine does not seem to be an adequate substitute for glucagon in the treatment of severe hypoglycemia. The effectiveness of glucagon in reversing hypoglycemia and its side effects of nausea and vomiting are likely related to the markedly supraphysiologic plasma levels achieved with the standard intramuscular dose.
Concordance for Type 1 Diabetes in Identical Twins Is Affected by Insulin Genotype
Authors: Metcalfe Karl A. , Hitman Graham A. , Rowe Rachel E. , Hawa Mohammed , Huang Xiaojian , Stewart Timothy , Leslie R. David G.
Published: March 2007

OBJECTIVE—Monozygotic twins are usually discordant (only one twin affected) for type 1 diabetes. Discordance for disease between such twins implies a role for nongenetically determined factors but could also be influenced by a decreased load of diabetes susceptibility genes. The aim of this study was to determine whether two susceptibility genes were less prevalent in discordant twins compared with concordant twins.

RESEARCH DESIGN AND METHODS—We studied 77 monozygotic twin pairs (INS), 40 concordant and 37 discordant, for type 1 diabetes at polymorphism of the insulin gene region on chromosome 11p and HLA-DQBI.

RESULTS—The disease-associated INS genotype (Hph I) was identified in 87.5% of the concordant twins but only in 59.5% (P = 0.005) of the discordant twins. Neither DQB1*0201 nor DQB1*0302 was seen in 2 of 40 (5%) concordant twins compared with 8 of 37 (22%) discordant twins (P = 0.04). No statistical differences were seen between concordant and discordant twins at individual alleles of DQB1. Combining insulin and DQ data, 5% of concordant twins compared with 32.4% of discordant twins had neither DQB1*0201/DQB1*0302 nor the high-risk Hph I INS “++” genotype (P = 0.002).

CONCLUSIONS—We conclude that the possession of the high-risk Hph I insulin genotype increases the likelihood of identical twins being concordant for type 1 diabetes and that the “load” of both major histocompatibility complex (MHC) and non-MHC susceptibility genes has an impact on the disease penetrance of type 1 diabetes.
Long-Term Oral l-Arginine Administration Improves Peripheral and Hepatic Insulin Sensitivity in Type 2 Diabetic Patients
Authors: Piatti PierMarco , Monti Lucilla D. , Valsecchi Gianpietro , Magni Fulvio , Setola Emanuela , Marchesi Federica , Galli-Kienle Marzia , Pozza Guido , Alberti K. George M.M.
Published: March 2007

OBJECTIVE—The aim of this study was to evaluate whether long-term administration of l-arginine acting through a normalization of NO/cyclic-guanosine-3′,5′-cyclic monophosphate (cGMP) pathway was able to ameliorate peripheral and hepatic insulin sensitivity in 12 lean type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—A double-blind study was performed for 3 months. In the first month, patients were treated with their usual diet. Then they were randomly allocated into two groups. In group 1, patients were treated with diet plus placebo (orally three times per day) for 2 months. In group 2 patients were treated for 1 month with diet plus placebo (orally, three times per day) and then for 1 month with diet plus l-arginine (3 g three times per day). At the end of the first and the second month of therapy, patients underwent a euglycemic-hyperinsulinemic clamp combined with [6,6-2H2]glucose infusion. A total of 10 normal subjects underwent the same test as control subjects.

RESULTS—In group 1, no changes in basal cGMP levels, systolic blood pressure, forearm blood flow, glucose disposal, and endogenous glucose production were observed throughout. In group 2, l-arginine normalized basal cGMP levels and significantly increased forearm blood flow by 36% and glucose disposal during the clamp by 34%, whereas it decreased systolic blood pressure and endogenous glucose production by 14 and 29%, respectively. However, compared with normal subjects, l-arginine treatment was not able to completely overcome the defect in glucose disposal.

CONCLUSIONS—l-Arginine treatment significantly improves but does not completely normalize peripheral and hepatic insulin sensitivity in type 2 diabetic patients.
Family Characteristics and Life Events Before the Onset of Autoimmune Type 1 Diabetes in Young Adults
Authors: Littorin Bengt , Sundkvist Göran , Nyström Lennarth , Carlson Anita , Landin-Olsson Mona , Östman Jan , Arnqvist Hans J. , Björk Elisabeth , Blohmé Göran , Bolinder Jan , Eriksson Jan W. , Scherstén Bengt , Wibell Lars
Published: March 2007

OBJECTIVE—To elucidate whether family characteristics and stressful life events were associated with onset of autoimmune type 1 diabetes in young adults.

RESEARCH DESIGN AND METHODS—This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of newly diagnosed patients aged 15–34 years. Patients clinically classified as type 1 diabetic with antibodies to islet cells and/or to GAD65 were compared with age- and sex-matched control subjects via questionnaire. The questionnaire covered diabetes heredity, social environment, educational level, and life events experienced during the 12 months before diagnosis.

RESULTS—The rate of response was 82% for the diabetic patients and 65% for the control subjects. Questionnaires from 349 diabetic patients and 979 control subjects were considered. Diabetes in relatives was more frequent in the patients (odds ratio [OR]2.6) who were born in Sweden and whose mothers were of Swedish origin. No major stress factors were detected in the diabetic patients; however, in comparison with the control subjects, the diabetic patients had experienced fewer conflicts with their parents and had less often broken contacts with friends.

CONCLUSIONS—Young adults with recent-onset type 1 diabetes were more exposed to heredity for diabetes, but no major prediabetic stress factors were detected. Our study does not directly support the concept that psychosocial stressful life events are involved in the development of autoimmune type 1 diabetes in young adults.
Prevalence of Diabetes in Care Home Residents
Authors: Sinclair Alan J. , Gadsby Roger , Penfold Sue , Croxson Simon C.M. , Bayer Antony J.
Published: March 2007

OBJECTIVE—To determine the prevalence of known and undetected diabetes diagnosed either by an elevated fasting baseline sample or by a 2-h post–glucose load sample in a group of residents of care homes in an urban-district setting.

RESEARCH DESIGN AND METHODS—We completed individual interviews with patients and caregivers in 30 care homes (both residential and nursing homes) in two metropolitan districts of Birmingham, West Midlands, U.K. All care homes were under the supervision of primary care physicians (general practitioners). We carried out 75-g oral glucose tolerance tests (OGTTs) in consenting residents without previous known diabetes. Criteria for diagnosis of diabetes were obtained from the World Health Organization (1998) and the American Diabetes Association (1997).

RESULTS—Of 636 residents available for study, 76 residents (12.0%) were known to have diabetes; of the 560 remaining residents, 286 either refused to participate or were deemed too ill or unavailable to undergo testing. Complete data on 274 OGTTs were obtained (median age 83 years, range 45–101). A total of 46 subjects were diagnosed as having diabetes and 94 as having impaired glucose tolerance. Allowing for subjects who refused or were unable to participate, the calculated total prevalence (which includes known and newly detected diabetes) was 26.7% (95% CI 21.9–32.0). The calculated overall prevalence of impaired glucose tolerance was 30.2% (25.2–35.6).

CONCLUSIONS—In a group of care home residents not known to have diabetes and able to undergo testing, a substantial proportion have undetected diabetes based on a 2-h postglucose load. These residents warrant further study as they may be at higher cardiovascular risk and require an intervention.
The Prevalence of Comorbid Depression in Adults With Diabetes
Authors: Anderson Ryan J. , Freedland Kenneth E. , Clouse Ray E. , Lustman Patrick J.
Published: March 2007

OBJECTIVE—To estimate the odds and prevalence of clinically relevant depression in adults with type 1 or type 2 diabetes. Depression is associated with hyperglycemia and an increased risk for diabetic complications; relief of depression is associated with improved glycemic control. A more accurate estimate of depression prevalence than what is currently available is needed to gauge the potential impact of depression management in diabetes.

RESEARCH DESIGN AND METHODS—MEDLINE and PsycINFO databases and published references were used to identify studies that reported the prevalence of depression in diabetes. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. We used χ2 statistics and odds ratios (ORs) to assess the rate and likelihood of depression as a function of type of diabetes, sex, subject source, depression assessment method, and study design.

RESULTS—A total of 42 eligible studies were identified; 20 (48%) included a nondiabetic comparison group. In the controlled studies, the odds of depression in the diabetic group were twice that of the nondiabetic comparison group (OR = 2.0, 95% CI 1.8–2.2) and did not differ by sex, type of diabetes, subject source, or assessment method. The prevalence of comorbid depression was significantly higher in diabetic women (28%) than in diabetic men (18%), in uncontrolled (30%) than in controlled studies (21%), in clinical (32%) than in community (20%) samples, and when assessed by self-report questionnaires (31%) than by standardized diagnostic interviews (11%).

CONCLUSIONS—The presence of diabetes doubles the odds of comorbid depression. Prevalence estimates are affected by several clinical and methodological variables that do not affect the stability of the ORs.
Declining Insulin Requirement in the Late First Trimester of Diabetic Pregnancy
Authors: Jovanovic Lois , Knopp Robert H. , Brown Zane , Conley Mary R. , Park Eunsik , Mills James L. , Metzger Boyd E. , Aarons Jerome H. , Holmes Lewis B. , Simpson Joe L. ,   and the National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study Group
Published: March 2007

OBJECTIVE—To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin requirement.

RESEARCH DESIGN AND METHODS—We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic women in the Diabetes in Early Pregnancy Study (DIEP) with accurate gestational dating, regular glucose monitoring, daily insulin-dose recording, and monthly glycohemoglobin measurements.

RESULTS—In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was observed between weeks 3 and 7 (P = 0.000), followed by a significant 9% decline from week 7 through week 15 (P = 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7–8 and ending weeks 11–12 (P = 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and 11 (median), and 8 and 9 (most frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women based on their glycohemoglobin values: <2 SDs above the mean of a normal population (subgroup 1), 2–4 SDs (subgroup 2), and >4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 (P = 0.002) and subgroups 2 and 3 together (P = 0.003). Similarly, women with BMI >27.0 had a greater initial insulin rise and then fall compared with leaner women.

CONCLUSIONS—Observations in the DIEP cohort disclose a mid–first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include overinsulinization of previously poorly controlled diabetes, a transient decline in progesterone secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of gestation.
Effect of Metformin in Pediatric Patients With Type 2 Diabetes
Authors: Jones Kenneth Lee , Arslanian Silva , Peterokova Valentina A. , Park Jong-Soon , Tomlinson Mark J.
Published: March 2007

OBJECTIVE—Metformin is the most commonly prescribed oral antidiabetic agent in the U.S. for adults with type 2 diabetes. The incidence of type 2 diabetes in children has increased dramatically over the past 10 years, and yet, metformin has never been formally studied in children with type 2 diabetes.

RESEARCH DESIGN AND METHODS—This study evaluated the safety and efficacy of metformin at doses up to 1,000 mg twice daily in 82 subjects aged 10–16 years for up to 16 weeks in a randomized double-blind placebo-controlled trial from September 1998 to November 1999. Subjects with type 2 diabetes were enrolled if they had a fasting plasma glucose (FPG) levels ≥7.0 and ≤13.3 mmol/l (≥126 and ≤240 mg/dl), HbA1c ≥7.0%, stimulated C-peptide ≥0.5 nmol/l (≥1.5 ng/ml), and a BMI >50th percentile for age.

RESULTS—Metformin significantly improved glycemic control. At the last double-blind visit, the adjusted mean change from baseline in FPG was −2.4 mmol/l (−42.9 mg/dl) for metformin compared with +1.2 mmol/l (+21.4 mg/dl) for placebo (P < 0.001). Mean HbA1c values, adjusted for baseline levels, were also significantly lower for metformin compared with placebo (7.5 vs. 8.6%, respectively; P < 0.001). Improvement in FPG was seen in both sexes and in all race subgroups. Metformin did not have a negative impact on body weight or lipid profile. Adverse events were similar to those reported in adults treated with metformin.

CONCLUSION—Metformin was shown to be safe and effective for treatment of type 2 diabetes in pediatric patients.
Fetal Growth Spurt and Pregestational Diabetic Pregnancy
Authors: Wong Shell Fean , Chan Fung Yee , Oats Jeremy J.N. , McIntyre David H.
Published: March 2007

OBJECTIVE—To assess the timing of fetal growth spurt among pre-existing diabetic pregnancies (types 1 and 2) and its relationship with diabetic control. To correlate fetal growth acceleration with factors that might influence fetal growth.

RESEARCH DESIGN AND METHODS—This retrospective study involved all pregestational diabetic pregnancies delivered at a tertiary obstetric hospital in Australia between 1 January 1994 and 31 December 1999. Pregnancies with major congenital fetal anomalies, multiple pregnancies, small-for-gestational-age pregnancies (<10th centile), and those that were terminated before 20 weeks were excluded. In this cohort, pregnancies delivered at term had at least four ultrasound scans performed. The first scans were performed before 14 weeks of gestation and were regarded as dating scans. Abdominal circumference measurements were retrieved from the ultrasound reports. The z-scores for abdominal circumferences, according to the gestational age, were calculated. The gestations when the ultrasound scans were performed were stratified at four weekly intervals beginning at 18 weeks and continuing through the rest of the study. Majority of these diabetic pregnancies had ultrasound scans performed at 18, 28, 32, and 36 weeks. The abdominal circumference z-scores for pregnancies with large-for-gestational-age (LGA) babies (>90th centile for gestation) were compared with babies with normal birth weights.

RESULTS—A total of 101 diabetic pregnancies were included. Diabetic mothers, who had LGA babies, had significantly higher prepregnancy body weight and BMI (P < 0.05). There were no differences in maternal age or parity among the two groups. There were also no differences in the first-, second-, and third-trimester HbA1c levels between the two groups. The abdominal circumference z-scores were significantly higher for LGA babies from 18 weeks and thereafter. The differences increased progressively as the gestation advanced. Maximum difference was noted in the third trimester (30–38 weeks).

CONCLUSIONS—Fetal growth acceleration in LGA fetuses of diabetic mothers starts in the second trimester, from as early as 18 weeks. In this study, glucose control did not appear to have a direct effect on the incidence of LGA babies, and such observation might result from the effects of other confounding factors.
Inside Guidelines
Authors: Burgers Jako S. , Bailey Julia V. , Klazinga Niek S. , Van der Bij Akke K. , Grol Richard , Feder Gene ,   for the AGREE Collaboration
Published: March 2007

OBJECTIVE—To compare guidelines on diabetes from different countries in order to examine whether differences in recommendations could be explained by use of different research evidence.

RESEARCH DESIGN AND METHODS—We analyzed 15 clinical guidelines on type 2 diabetes from 13 countries using qualitative methods to compare the recommendations and bibliometric methods to measure the extent of overlap in citations used by different guidelines. A further qualitative analysis of recommendations and cited evidence for two specific issues in diabetes care explored the apparent discrepancy between recommendations and evidence.

RESULTS—The recommendations made in the guidelines were in agreement about the general management of type 2 diabetes, with some important differences in treatment details. There was little overlap in evidence cited by the guidelines, with 18% (185/1,033) of citations shared with any other guideline, and only 10 studies (1%) appearing in six or more guidelines. The measurable overlap in evidence between guidelines increases if multiple publications from the same study and the use of reviews are taken into account. Research originating from the U.S. predominated (40% of citations); however, nearly all (11/12) guidelines were significantly more likely to cite evidence originating from their own countries.

CONCLUSIONS—Despite the variation in cited evidence and preferential citation of evidence from a guideline’s country of origin, we found a high degree of international consensus in recommendations made for the clinical care of type 2 diabetes. The influence of professional bodies such as the American Diabetes Association may be an important factor in explaining international consensus. Globalization of recommended management of diabetes is not a simple consequence of the globalization of research evidence.
Influence of Metabolic Control on Splanchnic Glucose Uptake, Insulin Sensitivity, and the Time Required for Glucose Absorption in Patients With Type 1 Diabetes
Authors: Georg Petra , Kautzky-Willer Alexandra , Mahdjoobian Katja , Hofer Astrid , Prager Rudolf , Pacini Giovanni , Ludvik Bernhard H.
Published: March 2007

OBJECTIVE—The relationship between splanchnic glucose uptake (SGU) after oral glucose administration and metabolic control in type 1 diabetic patients is controversial. We estimated SGU as well as peripheral glucose uptake and the time required for glucose absorption by a validated method, the oral glucose (OG) clamp, in type 1 diabetic patients with different levels of long-term glycemic control.

RESEARCH DESIGN AND METHODS—An OG clamp (which combines a hyperinsulinemic clamp [120 mU · m−2 · min−1] with an OR load [75 g] during steady-state glucose uptake) was performed in eight type 1 diabetic patients with good metabolic control (DG) (HbA1c 6.1 ± 0.2%, BMI 23.1 ± 0.7 kg/m2), eight type 1 diabetic patients with poor metabolic control (DP) (HbA1c 8.5 ± 0.3%, BMI 25.4 ± 1.4 kg/m2), and eight healthy matched control subjects (C) (HbA1c 5.1 ± 0.1%, BMI 25 ± 1.3 kg/m2) to determine SGU, glucose uptake, and glucose absorption.

RESULTS—Glucose uptake calculated from 120 to 180 min during the clamp was 9.13 ± 0.55 mg · kg−1 · min−1 in C, 8.18 ± 0.71 mg · kg−1 · min−1 in DG, and 7.42 ± 0.96 mg · kg−1 · min−1 in DP (NS). Glucose absorption was 140 ± 6 min in C, 156 ± 4 min in DG, and 143 ± 7 min in DP (NS). The respective calculated SGU was 14.5 ± 5.6% in C, 17.8 ± 3.1% in DG, and 18.8 ± 4.2% in DP (NS) and did not correlate with HbA1c values.

CONCLUSIONS—Peripheral glucose uptake, SGU after oral glucose administration, and the glucose absorption time were not different in type 1 diabetic patients independent of glycemic control when compared with healthy subjects.
Control of Postprandial Hyperglycemia
Authors: Carroll Mary F. , Izard Ahmad , Riboni Katrina , Burge Mark R. , Schade David S.
Published: March 2007

OBJECTIVE—This study was designed to compare the efficacy of acute premeal administration of glipizide versus nateglinide in controlling postprandial hyperglycemia in subjects with non-insulin-requiring type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 20 subjects (10 female, 10 male) with non-insulin-requiring type 2 diabetes were admitted overnight to the General Clinical Research Center on four occasions. In random order, 10 mg glipizide (30 min premeal), 120 mg nateglinide (15 min premeal), 10 mg glipizide plus nateglinide (30 and 15 min premeal, respectively), or placebo pills (30 and 15 min premeal) were administered in a double-blind fashion before a standardized breakfast. Blood was drawn for analysis of glucose, insulin, and C-peptide at −0.05, 0, 0.5, 1, 2, 3, and 4 h relative to the meal.

RESULTS—The subjects were aged 56 ± 2 years and were moderately obese (BMI 31 ± 1 kg/m2), with a mean HbA1c of 7.4 ± 0.4%. The peak postprandial glucose excursion above baseline was higher with placebo (6.1 ± 0.5 mmol/l) than glipizide (4.3 ± 0.6 mmol/l, P = 0.002), nateglinide (4.2 ± 0.4 mmol/l, P = 0.001), or glipizide plus nateglinide (4.1 ± 0.5 mmol/l, P = 0.001). The area under the curve for the glucose excursion above baseline was also higher with placebo (14.1 ± 1.8 mmol/h · l) compared with glipizide (6.9 ± 2.4 mmol/h · l, P = 0.002), nateglinide (9.7 ± 2 mmol/h · l, P = 0.004), or glipizide plus nateglinide (5.6 ± 2.2 mmol/h · l, P < 0.001). Peak and integrated glucose excursions did not differ significantly between glipizide and nateglinide. However, by 4 h postmeal, plasma glucose levels were significantly higher with nateglinide (9 ± 0.9 mmol/l) compared with the premeal baseline (7.8 ± 0.6 mmol/l, P = 0.04) and compared with the 4-h postprandial glucose level after administration of glipizide (7.6 ± 0.6 mmol/l, P = 0.02). Integrated postprandial insulin levels were higher with glipizide (1,556 ± 349 pmol/h · l) than nateglinide (1,364 ± 231 pmol/h · l; P = 0.03). Early insulin secretion, as measured by insulin levels at 30 min postmeal, did not differ between glipizide and nateglinide.

CONCLUSIONS—Acute premeal administration of nateglinide or glipizide has equal efficacy in controlling postbreakfast hyperglycemia in type 2 diabetes when each drug is administered at the optimum time before the meal. Glipizide causes a more pronounced and sustained postmeal insulin secretory response compared with nateglinide. Glipizide facilitates the return to near-fasting glucose levels at 4 h postmeal, but with the possible risk of increased frequency of postmeal hypoglycemia in drug-naive patients. The clinical decision to use glipizide versus nateglinide should be based on factors other than the control of postprandial hyperglycemia in type 2 diabetes.