Insulin dose reduction in dapagliflozin combination therapy for type 1 diabetes mellitus: the RISING-STAR study.

To clarify the frequency of hypoglycemia in patients with type 1 diabetes mellitus receiving dapagliflozin combination therapy to reduce their basal insulin dose. Sixty subjects were assigned to two groups according to their basal insulin-to-total daily dose (TDD) ratio: group A (basal insulin/TDD <40%) and group B (≥40%). Reduction of the basal insulin dose was instituted in group B, but not in group A. The number of hypoglycemic events per day and ketosis frequency were the primary and secondary endpoints, respectively. The hypoglycemia frequency before and after the intervention was 0.23 and 0.26 times/day in group A and 0.19 and 0.23 times/day in group B, respectively, with no significant difference between the groups. The total insulin dose reduction was approximately 10% in both groups. Ketosis frequency increased significantly after the intervention (from 0.013 to 0.086 times/day in group A and 0.013 to 0.059 times/day in group B). Time-in-range, mean amplitude of glycemic excursion, and glycated hemoglobin A1c improved in both groups. No significant difference in hypoglycemia frequency was observed between patients with and without reduction of the basal insulin dose. The combination therapy improved glycemic control and patient satisfaction regarding hyperglycemia. Nevertheless, adequate attention to ketosis is crucial.

Nutritional Status Assessed with Objective Data Assessment Correlates with a High-Risk Foot in Patients with Type 2 Diabetes.

Malnutrition and diabetes are likely to co-occur. There are few reports on the association between nutritional status and foot risk in patients with type 2 diabetes (T2D). Therefore, we aimed to investigate this relationship in this cross-sectional study. We investigated the relationships between objective data assessment (ODA), especially Controlling Nutritional Status (CONUT) score and foot risk, evaluated by the International Working Group on the Diabetic Foot (IWGDF), in consecutive patients with T2D. Patients were divided into groups 0 to 3 by IWGDF, and groups 1 to 3 were defined as high-risk groups. Among 469 patients, 42.6% (n = 200) of them had high-risk foot. Patients with high-risk foot were significantly older (71.2 ± 11.3 vs. 64.2 ± 13.4 years, p < 0.001) and had a longer duration of diabetes (18.0 ± 12.0 vs. 11.5 ± 10.0 years, p < 0.001) than those in the low-risk group. In the high-risk group, serum albumin level, total lymphocyte count, hemoglobin, and CONUT score were significantly worse, especially in older patients (≥75 years). Multivariate logistic regression analysis showed that there was a positive correlation between CONUT score and high-risk foot in older patients (OR, 1.37; 95% CI, 1.05−1.86; p = 0.021). Our results indicated that nutritional status, assessed by ODA, correlated with high-risk foot, especially in older patients with T2D.

Multicenter, Open-Label, 2-Arm, Pilot Trial for Safe Reduction of Basal Insulin Dose Combined with SGLT2 Inhibitor in Type 1 Diabetes Mellitus: Study Protocol for a RISING-STAR Trial.

BACKGROUND: The safe method of instructing insulin dose reduction in combination with SGLT2 inhibitors, dapagliflozin for patients with type 1 diabetes mellitus has not been clarified. In this study, we conducted a stratified, 2-arm, parallel comparative study with the primary endpoint of decreasing the frequency of hypoglycemia by instructing basal insulin dose reduction. METHODS: The study has a multicenter, open-label, 2-arm design; 60 type 1 diabetes mellitus patients are being recruited from 7 hospitals. Study subjects have been stratified into 2 groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects whose Basal/TDD ratio is <0.4 are instructed not to reduce Basal but to reduce bolus insulin dose by 10% (group A), and subjects with a Basal/TDD ratio >0.4 will be instructed to reduce Basal by 10% (group B). The primary outcome is the daily frequency of hypoglycemia during the intervention period (SGLT2 inhibitor administration), as determined by self-monitoring of blood glucose. We aimed to confirm a greater reduction in frequency of hypoglycemia in group B (reduced Basal), than in group A (non-reduction of Basal and reduced insulin effect levels by 10%). Baseline hypoglycemia was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of .05 for a 1-sided t-test with a statistical power at 80% is determined. When the sample size is 26 patients in 1 group, the percentage increase in hypoglycemia exceeds 60%, and the sample size is considered sufficient. DISCUSSION: In this pilot study, we assumed that, given a sufficient Basal, hypoglycemia would be more frequent in patients with type 1 diabetes when combined with SGLT2 inhibitors, provided the Basal was not reduced.

The Value of Interleukin-6 among Several Inflammatory Markers as a Predictor of Respiratory Failure in COVID-19 Patients.

Patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure within a short period during the clinical course. It is essential to predict respiratory deterioration in the short term. We investigated the use of inflammatory markers to predict respiratory distress within three days from their analysis in COVID-19 patients. This retrospective observational study included 81 patients admitted with COVID-19. Patients were divided into two groups according to whether the maximum fraction of inspired oxygen (FiO2) for three days from the blood marker measurements was ≥0.4 (high FiO2 group; HFG) or <0.4 (low FiO2 group; LFG). Interleukin-6 (IL-6), C-reactive protein (CRP), lactate dehydrogenase (LDH), white blood cell, D-dimer, and creatinine levels were compared between the two groups. The levels of all markers were significantly higher in HFG patients. Areas under the receiver operating characteristic curve of IL-6, CRP, and LDH had high values of 0.85, 0.82, and 0.81, respectively. The odds ratio of IL-6 which was crude and adjusted for dexamethasone administration initiated before laboratory measurement, showed the high value of 29.1 (5.6-295.6) and 53.9 (4.5-3242.8), respectively. IL-6 can be used as a reliable marker for predicting respiratory illness within three days after assessment.

Trigger finger is associated with risk of incident cardiovascular disease in individuals with type 2 diabetes: a retrospective cohort study.

INTRODUCTION: Trigger finger is one of the complications affecting the upper extremity in patients with diabetes. Diabetes is also a well-known risk factor that predisposes individuals to cardiovascular diseases (CVDs). This retrospective cohort study aimed to establish the association between trigger finger and the patients with incident CVD with type 2 diabetes. MATERIALS AND METHODS: Trigger finger was diagnosed by palpating a thickened tendon during flexion or on the manifestation of a locking phenomenon during extension or flexion of either finger. The relationship between trigger finger and other clinical parameters or complications of diabetes was examined by a comparative analysis. Cox regression analysis was used to evaluate the association between trigger finger and incidence of CVD. We calculated the propensity scores using sex, body mass index, age, smoking status, duration of diabetes, estimated glomerular filtration rate, hypertension, dyslipidemia, and hemoglobin A1c as the number of patients with incident CVD during the follow-up period was low. RESULTS: Among the 399 patients with type 2 diabetes, 54 patients had trigger finger. Patients with trigger finger were significantly older in age and had been suffering from diabetes for a longer duration. They also displayed worse renal function and glycemic control, along with a higher incidence of hypertension, neuropathy and nephropathy. During the average 5.66±1.12 years of follow-up, a total of 18 incidents occurred. According to the Cox regression analysis, trigger finger was shown to be associated with enhanced risk of the incidence of CVD after adjustment for the covariates (adjusted HR=3.33 (95% CI 1.25 to 8.66), p=0.017). CONCLUSIONS: Trigger finger is associated with the risk of incident CVD in patients with type 2 diabetes. Thus, clinicians must consider these factors at the time of diagnosis of such patients.

Limited joint mobility of the hand correlates incident hospitalisation with infection in patients with type 2 diabetes.

AIM: Limited joint mobility (LJM) of the hand is one of the important complications of diabetes. Diabetes is a risk factor for hospitalisation with infection. This study investigated the relationship between LJM of the hand and the incidence of hospitalisation with infection in type 2 diabetic patients. MATERIALS AND METHODS: LJM of hand was defined as the 'prayer sign' or 'table test'. The association between LJM of the hand and incident hospitalisations was evaluated using Cox regression analysis. The number of incident hospitalisations was small over the course of the study, which we compensated for by calculating propensity scores using age, body mass index, sex, duration of diabetes, creatinine, smoking status, haemoglobin A1c and dyslipidaemia. RESULTS: In this retrospective cohort study of 502 patients with type 2 diabetes, 102 patients had LJM of the hand. These patients were, on average, older and had worse renal function and glycaemic control, and a higher proportion of microangiopathy significantly. During the study period, 56 patients were hospitalised with infection. A Cox regression analysis showed that LJM of the hand was associated with an increased probability of incident hospitalisation with infection after adjustment for covariates (HR = 1.65 [95% CI 1.60-1.70], p < 0.001). CONCLUSIONS: Our results reveal that LJM of the hand is associated with incident of hospitalisation with infection. A diagnosis of LJM of the hand might, therefore, be a useful indicator for assessing the risk of hospitalisation with infection in type 2 diabetic patients.

Malnutrition assessed by controlling nutritional status is correlated to carotid atherosclerosis in patients with type 2 diabetes.

Diabetes and malnutrition sometimes overlap. Little is known about the relationship between malnutrition and subclinical atherosclerosis in patients with type 2 diabetes. This cross-sectional study investigated this relationship in patients with type 2 diabetes. We evaluated the relationships between malnutrition assessed by controlling nutritional status (CONUT) score and subclinical atherosclerosis assessed by carotid intima-media thickness (IMT) and carotid plaque scores in 461 consecutive patients with type 2 diabetes. Nutritional assessment indicated that 38% of patients were malnourished (CONUT ≥3). Carotid IMT and carotid plaque scores were significantly higher in patients with malnutrition. Multivariate linear regression analyses revealed that a high CONUT score (CONUT ≥3) was correlated with mean IMT (ß = 0.196, p = 0.043) and max IMT (ß = 0.243, p = 0.011) in patients taking statins and was also correlated with mean IMT (ß = 0.287, p = 0.004), max IMT (ß = 0.308, p = 0.002), and plaque score (ß = 0.190, p = 0.044) in patients not taking statins after adjusting for age, sex, duration of diabetes, body mass index, hemoglobin A1c, creatine, smoking, and hypertension. Our results demonstrate a relationship between malnutrition and subclinical atherosclerosis in patients with type 2 diabetes.

Platelet to lymphocyte ratio correlates with diabetic foot risk and foot ulcer in patients with type 2 diabetes.

Diabetic foot ulcer is a major complication in patients with diabetes. Platelet-lymphocyte ratio (PLR) has been reported to have a predictive effect to some diabetic complications in recent years. However, it has not been fully elucidated about the relationship between diabetic foot risk or diabetic foot ulcer and PLR in patients with type 2 diabetes. Therefore, we aimed to evaluate this relationship. In this cross-sectional study, we evaluated the relationships between patient's diabetic foot risk with the criteria of the International Working Group on the Diabetic Foot (IWGDF) and prevalent foot ulcer, and PLR in 453 consecutive patients with type 2 diabetes. Propensity score analysis was used to adjust the difference of covariates; age, sex, duration of diabetes, body mass index (BMI), HbA1c, current smoking, hypertension, dyslipidemia, neuropathy, PAD, foot deformity and history of foot ulcers. PLR was higher in patients with high risk diabetic foot or foot ulcer (117 ± 40 vs. 107 ± 31, p = 0.003 and 148 ± 65 vs. 113 ± 56, p < 0.001). A receiver-operating characteristic curve demonstrated that PLR of 130.6 constitutes the cut-off value for prevalent foot ulcer with sensitivity 0.85 and specificity 0.70. Multivariate logistic regression analysis revealed that PLR was positively correlated with prevalent foot ulcer (odds ratio, 1.02; 95% confidence interval 1.01-1.04, p = 0.003) after adjusted for several variables with propensity score analysis. Our results demonstrated that PLR can be a marker for high risk diabetic foot and diabetic foot ulcer in patients with type 2 diabetes.

Neutrophil-lymphocyte ratio correlates with limited joint mobility of hand in patients with type 2 diabetes.

Limited joint mobility (LJM) of hand, which is one of the complications of diabetic hand, is associated with diabetic micro- and macroangiopathy although the precise pathogenesis is not completely understood. Neutrophil-lymphocyte ratio (NLR), a simple and novel inflammatory marker, has been reported to have a predictive effect to some diabetic complications in recent years. However, it is not elucidated about the relationship between LJM of hand and NLR in patients with type 2 diabetes. We evaluated the relationships between LJM of hand and NLR in 335 consecutive patients with type 2 diabetes in this cross-sectional study. LJM of hand was diagnosed by a 'prayer sign' or 'table test'. LJM of hand was present in 80 patients. The patients with LJM of hand had significantly older age, longer duration of diabetes, worse renal function, and higher proportion of diabetic neuropathy, retinopathy and nephropathy. NLR in patients with LJM of hand was higher than that in patients without LJM of hand (2.54 ± 1.46 vs. 2.11 ± 1.04, p = 0.004). Multivariate logistic regression analysis revealed that LJM of hand was positively correlated with NLR (odds ratio, 1.31; 95% confidence interval 1.03-1.69, p = 0.027) after adjustment for age, sex, duration of diabetes, body mass index, hemoglobin A1c, hypertension and dyslipidemia. Our results demonstrate a positive relation between LJM of hand and NLR in patients with type 2 diabetes.

Relationship between limited joint mobility of hand and carotid atherosclerosis in patients with type 2 diabetes.

AIM: Limited joint mobility (LJM) of hand, which is one of a complication of diabetic hand, has a close association with diabetic microangiopathy. However, it remains to be elucidated about the relationships between LJM of hand and subclinical atherosclerosis in patients with type 2 diabetes. Therefore, we conducted a cross-sectional study to evaluate the relationships between LJM of hand and carotid intima-media thickness (IMT) and plaque score in patients with type 2 diabetes. METHODS: We evaluated the relationships between LJM of hand, and carotid IMT and plaque score, evaluated by carotid ultrasound examination, in 341 consecutive patients with type 2 diabetes. LJM of hand was diagnosed using a 'prayer sign' or 'table test'. RESULTS: LJM of hand was present in 72 patients. Carotid IMT and plaque score were higher in patients with LJM of hand than those in patients without (1.45±0.66vs. 1.14±0.68mm, P=0.013 and 8.0±5.3vs. 5.4±4.8mm, P<0.001). Multivariate linear regression analysis revealed that LJM of hand was positively correlated with plaque score (ß=0.423, P=0.043) after adjusted for age, sex, durations of diabetes, body mass index, hemoglobin A1c, creatinine, uric acid, smoking, hypertension and dyslipidemia. CONCLUSIONS: Our results demonstrate a relation between LJM of hand and subclinical atherosclerosis, especially plaque score, in patients with type 2 diabetes. Diagnosis of diabetic hand is simple and non-invasive, and thus is a useful method for assessment of subclinical atherosclerosis in patients with type 2 diabetes.

Relationship between limited joint mobility of the hand and diabetic foot risk in patients with type 2 diabetes.

BACKGROUND: Foot ulceration is a serious problem for patients with type 2 diabetes (T2D), and the early detection of risks for this condition is important to prevent complications. The present cross-sectional study in T2D patients determined the relationship between limited joint mobility (LJM) of the hand and diabetic foot risk classified using the criteria of the International Working Group on the Diabetic Foot (IWGDF). METHODS: Relationships between LJM of the hand and foot risk according to IWGDF category, HbA1c, age, body mass index, blood pressure, estimated glomerular filtration (eGFR), and diabetic complications (including diabetic peripheral neuropathy [DPN] and peripheral arterial disease [PAD]) were evaluated in 528 consecutive T2D patients. Poor glycemic control was defined as HbA1c ≥ 7%. RESULTS: Patients with LJM of the hand were older and had a longer duration of diabetes, a higher prevalence of diabetic complications, including DPN and PAD, and a higher IWDGF category (all P < 0.001). Multivariate logistic regression analysis revealed that the foot risk assessed with IWDGF category was correlated with age (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01-1.06; P = 0.001), poor glycemic control (OR 1.66; 95% CI 1.00-2.77; P = 0.04), eGFR (OR 0.98; 95% CI 0.97-0.99; P = 0.02), and the presence of LJM of the hand (OR 3.86; 95% CI 2.21-6.86; P < 0.001). CONCLUSIONS: The results demonstrate a correlation between LJM of the hand and foot risk. Diagnosis of diabetic hand is simple and non-invasive, and is thus a useful method for assessing the risk of diabetic foot in T2D patients.

Replacement of neutral protamine Hagedorn insulin with the long-acting insulin analogue, detemir, improves glycemic control without weight gain in basal-bolus insulin therapy in Japanese patients with type 1 diabetes.

UNLABELLED: Aims/Introduction: The aim of the present study was to evaluate the efficacy of replacing neutral protamine Hagedorn insulin (NPH) with the long-acting insulin analogue, detemir, in clinical practice. MATERIALS AND METHODS: We carried out a retrospective study to compare the effects of replacing NPH with detemir in basal-bolus insulin therapy in Japanese patients with type 1 diabetes. A total of 19 patients were enrolled in the study, and changes in hemoglobin A1c (HbA1c), insulin dose, bodyweight, fasting blood glucose levels (FBG), within-patient variability in FBG and prevalence in hypoglycemia were monitored for 12 weeks before replacement and during three periods after replacement; 1-12 weeks (period 1), 13-24 weeks (period 2) and 25-36 weeks (period 3). RESULTS: HbA1c values improved significantly in periods 2 and 3. Despite the total insulin dose remaining unchanged throughout the study, the basal insulin dose increased from 0.24 to 0.27 IU/kg/day in period 2 and 0.28 IU/kg/day in period 3. Bodyweight decreased from 61.8 to 60.8 kg in period 1, whereas FBG improved throughout the study. Within-patient variability in FBG was lower with detemir treatment than with NPH, despite the number of hypoglycemic episodes increasing significantly after replacement. CONCLUSIONS: These findings show that the weight loss observed in patients was independent of the reduction in calorie intake resulting from less frequent hypoglycemic attacks. In Japanese patients with diabetes who received NPH, replacing NPH with detemir led to improvements in glycemic control without any weight gain. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00066.x, 2010).

Clinical and genetic characteristics of diabetic patients with high-titer (>10,000 U/ml) of antibodies to glutamic acid decarboxylase.

We investigated the clinical aspects and genetic background of 13 diabetic patients with high-titers (>10,000 U/ml) of anti-glutamic acid decarboxylase antibody (Group A) and compared these 28 middle-aged (35-51 years, Group B) and 13 elderly (66-79 years, Group C) patients with anti-GAD(+) (<1100 U/ml) who were diagnosed initially as having type 2 diabetes. The mean age and mean age at onset of Group A were 70.8 +/- 3.9 years (range, 64-78) and 50.4 +/- 5.4 years (range, 43-61), respectively. In Group A, the prevalence of insulin-deficient patients was significantly lower (30.8%, 4 of 13) than in Group C (96.3%, 27 of 28, P < 0.001). Patients in Group A had a significantly longer interval between the clinical onset of diabetes to initiation insulin therapy (21.8 +/- 2.3 years) compared to patients in both Group B (1.8+/-1.1 years, P < 0.001) and Group C (14.8 +/- 7.1 years, P = 0.049). The frequency of DRB1*0405-DQB1*0401/DRB1*1502-DQB1*0601 or DRB*1501-DQB*0602 heterozygous genotypes in Group A (53.8%, 7 of 13) was significantly higher than in both Group B (3.6%, 1 of 28, P < 0.01) and Group C (7.7%, 1 of 13, P < 0.05). Compared with Group B, Group A had an increased frequency of the TNFA-U01 haplotype and the IL-10 -592 C allele (TNFA-U01; 53.8% versus 30.4%, P = 0.05 and IL-10 -592 C; 57.7% versus 33.9 %, P = 0.042). All sera from Group A reacted with GAD(65) protein on Western blots. We conclude that adult-onset diabetic patients with a high-titer of anti-GDAab differ from patients with latent autoimmune diabetes mellitus in adult (LADA) with respect to beta-cell function, cellular autoimmunity and genetic background. Our study also showed that high-titers of antibodies to glutamic acid decarboxylase (anti-GADab) were not predictive of later development of insulin deficiency in adult and/or elderly patients with type 2 diabetes. Furthermore, our results suggest that HLA-DRB1*1502-DQB1*0601 or DRB1*1501-DQB1*0602/DRB1*0405-DQB1*0401 heterozygous genotypes may be associated with high production of anti-GADab that recognizes the linear epitope(s) on the GAD(65) protein.

Short-term exposure of high glucose concentration induces generation of reactive oxygen species in endothelial cells: implication for the oxidative stress associated with postprandial hyperglycemia.

Recent studies demonstrating a close relationship between postprandial hyperglycemia and the incidence of atherosclerotic cardiovascular disease prompted us to investigate the generation and source of reactive oxygen species (ROS) in endothelial cells stimulated by short-term exposure to a high glucose concentration. In addition, we investigated the effect of insulin on ROS production induced by high glucose concentration. Cultured bovine aortic endothelial cells demonstrated a significant increase in intracellular ROS generation after a 3-h exposure to 25 mM glucose (131.4% versus 5 mM glucose). This increased generation of ROS was suppressed by an inhibitor of NAD(P)H oxidase. Intracellular ROS production in cells exposed to 3 h of high glucose concentration was increased significantly by the presence of a physiological concentration of insulin. However, after a 1-h exposure to high glucose levels, ROS generation in cells incubated with insulin was only about 80% of that measured in cells incubated without insulin. The generation of intracellular nitric oxide (NO) resulting from an acute insulin effect may account for this difference. In conclusion, acute hyperglycemia itself may possibly cause endothelial oxidative stress in patients with postprandial hyperglycemia. Endothelial oxidative stress may be determined by the interaction between NO and superoxide generation.

In vivo functioning and transplantable mature pancreatic islet-like cell clusters differentiated from embryonic stem cell.

INTRODUCTION: Although the differentiation of embryonic stem (ES) cells to islet like clusters using differentiation method without employing gene transfer technique has been recently reported, neither endocrine granules in the cytoplasm nor in vivo function of differentiated islet like clusters has been demonstrated. AIMS: To investigate whether ES cells could be differentiated to mature islet like clusters which show in vivo function after transplantation as well as retain endocrine granules in the cytoplasm by electron microscopic observation. METHODOLOGY: In this experiment, using mouse embryonic stem (mES) cells as a model system for lineage specific differentiation, we tried to differentiate mES cells to pancreatic islet-like cell clusters (PICCs) through a series of treatments (4-step procedure). Differentiated PICCs were analyzed and characterized by various techniques, such as RT-PCR, immunohistochemistry, electron microscopic observation, in vitro static incubation test, and in vivo transplantation to diabetic animals. RESULTS: Differentiated islet-like cell clusters from ES cells using our newly developed method (four-step procedure) showed strong expression of essential specific genes to the endocrine pancreas and also specific genes to the exocrine pancreas demonstrating that these islet-like clusters were mature from the developmental biologic point of view. These differentiated cells clearly revealed many mature insulin secretory granules of pleomorphic shape in the cytoplasm as well as well-developed rough endoplasmic reticulum. In vitro study indicated that differentiated cells retain a potent insulin secretory responsiveness to glucose stimulation. Furthermore, the islet-like cell clusters significantly decreased high blood glucose levels almost to normal levels when grafted to streptozotocin-induced diabetic mice without induction of any teratoma formation after transplantation. CONCLUSION: Our results provide evidence that ES cells could differentiate to functioning and transplantable mature pancreatic islet-like cell clusters using our newly developed differentiation method without employing gene transfer technique. This study may lead to a basis for production of indefinite sources of islets that could be applicable for future clinical trial.

Leukocyte-endothelial cell adhesion molecule 1 (LECAM-1) polymorphism is associated with diabetic nephropathy in type 2 diabetes mellitus.

BACKGROUND/AIMS: Glomerular infiltration with monocytes/macrophages has been implicated in the pathogenesis of diabetic nephropathy. In this study, we evaluated the relationship between the genetic polymorphism in leukocyte-endothelial adhesion molecule-1 (LECAM-1) and diabetic nephropathy in patients with type 2 diabetes mellitus. METHODS: We determined the frequency of the LECAM-1 P213S genotype in 102 diabetic patients with diabetic nephropathy, 90 diabetic patients with no evidence of diabetic nephropathy, and 200 healthy control individuals. RESULTS: The frequency of the LECAM-1 213PP genotype and P allele in patients with diabetic nephropathy was significantly higher than that in patients without nephropathy (genotype 68% vs. 53%, chi(2)=6.78, P=.034; allele 83% vs. 72%, chi(2)=6.26, P=.012). The LECAM-1 P213 genotype was associated with a 1.86-fold increased risk for nephropathy independently of other risk factors. CONCLUSION: The data suggest that the LECAM-1 213PP genotype is a genetic risk factor for the development of nephropathy in type 2 diabetes mellitus.