Jae-Seung Yun

Presence of macroalbuminuria predicts severe hypoglycemia in patients with type 2 diabetes: a 10-year follow-up study.

OBJECTIVE We investigated the factors that might influence the development of severe hypoglycemia in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS From January 2000 to December 2002, patients with type 2 diabetes aged 25–75 years without chronic kidney disease (estimated glomerular filtration rate ≥60 mL/min/1.73 m2) were consecutively recruited (n = 1,217) and followed-up in January 2011 and May 2012. Severe hypoglycemia (SH) was defined as an event requiring the assistance of another person to actively administer glucose, hospitalization, or medical care in an emergency department. We used Cox proportional hazard regression analysis to test the association between SH episodes and potential explanatory variables. RESULTS After a median 10.4 years of follow-up, 111 (12.6%) patients experienced 140 episodes of SH, and the incidence was 1.55 per 100 patient-years. Mean age and duration of diabetes were 55.3 ± 9.8 and 9.8 ± 6.5 years, respectively. The incidence of SH events was higher in older patients (P < 0.001), in those with a longer duration of diabetes (P < 0.001), in those who used insulin (P < 0.001) and sulfonylurea (P = 0.003), and in those who had macroalbuminuria (P < 0.001) at baseline. Cox hazard regression analysis revealed that SH was associated with longer duration of diabetes and the presence of macroalbuminuria (normoalbuminuria versus macroalbuminuria: hazard ratio, 2.52; 95% CI 1.31–4.84; P = 0.006). CONCLUSIONS The development of SH was independently associated with duration of diabetes and presence of macroalbuminuria, even with normal renal function in patients with type 2 diabetes.

Cardiovascular Autonomic Dysfunction Predicts Severe Hypoglycemia in Patients With Type 2 Diabetes: A 10-Year Follow-up Study

OBJECTIVE The aim of this study was to investigate the development of severe hypoglycemia (SH) in the presence of cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS From January 2001 to December 2002, a total of 894 patients with type 2 diabetes were enrolled. A cardiovascular autonomic function test (AFT) was performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to Valsalva maneuver, and standing. From the results for each of the three tests (0 for normal, 1 for abnormal), a total AFT score of 1 was defined as early CAN, and an AFT score of ≥2 was defined as definite CAN. RESULTS The median follow-up time was 9.5 years. The mean age was 54.5 ± 10.1 years, and the mean duration of diabetes was 8.9 ± 6.3 years. One hundred ninety-six patients (31.4%) showed an abnormal cardiovascular AFT score at baseline. Sixty-two patients (9.9%) experienced 77 episodes of SH (1.33 per 100 patient-years). The number of SH events increased as the CAN score increased (23 patients [5.4%] with normal score; 17 patients [17.2%] with early CAN; and 22 patients [22.7%] with definite CAN; P for trends < 0.001). Cox proportional hazards regression analysis revealed that SH was associated with definite CAN (normal vs. definite CAN: hazard ratio 2.43 [95% CI 1.21–4.84]; P = 0.012). CONCLUSIONS Definite CAN was an independent prognostic factor for the development of SH in patients with type 2 diabetes.

Higher prevalence of metformin-induced vitamin B12 deficiency in sulfonylurea combination compared with insulin combination in patients with type 2 diabetes: a cross-sectional study.

Long-term and high-dose treatment with metformin is known to be associated with vitamin B12 deficiency in patients with type 2 diabetes. We investigated whether the prevalence of B12 deficiency was different in patients treated with different combination of hypoglycemic agents with metformin during the same time period. A total of 394 patients with type 2 diabetes treated with metformin and sulfonylurea (S+M group, n = 299) or metformin and insulin (I+M group, n = 95) were consecutively recruited. The vitamin B12 and folate levels were quantified using the chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12≤300 pg/mL without folate deficiency (folate>4 ng/mL). The mean age of and duration of diabetes in the subjects were 59.4±10.5 years and 12.2±6.7 years, respectively. The mean vitamin B12 level of the total population was 638.0±279.6 pg/mL. The mean serum B12 levels were significantly lower in the S+M group compared with the I+M group (600.0±266.5 vs. 757.7±287.6 pg/mL, P<0.001). The prevalence of vitamin B12 deficiency in the metformin-treated patients was significantly higher in the S+M group compared with the I+M group (17.4% vs. 4.2%, P = 0.001). After adjustment for various factors, such as age, sex, diabetic duration, duration or daily dose of metformin, diabetic complications, and presence of anemia, sulfonylurea use was a significant independent risk factor for B12 deficiency (OR = 4.74, 95% CI 1.41–15.99, P = 0.012). In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels.

Clinical Course and Risk Factors of Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus in Korea

Background We investigated clinical course and risk factors for diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 759 patients with T2DM without DR were included from January 2001 to December 2004. Retinopathy evaluation was performed at least annually by ophthalmologists. The severity of the DR was classified into five categories according to the International Clinical Diabetic Retinopathy Severity Scales. Results Of the 759 patients, 523 patients (68.9%) completed the follow-up evaluation. During the follow-up period, 235 patients (44.9%) developed DR, and 32 patients (13.6%) progressed to severe nonproliferative DR (NPDR) or proliferative DR (PDR). The mean duration of diabetes at the first diagnosis of mild NPDR, moderate NPDR, and severe NPDR or PDR were 14.8, 16.7, and 17.3 years, respectively. After adjusting multiple confounding factors, the significant risk factors for the incidence of DR risk in patients with T2DM were old age, longer duration of diabetes, higher mean glycosylated hemoglobin (HbA1c), and albuminuria. Even in the patients who had been diagnosed with diabetes for longer than 10 years at baseline, a decrease in HbA1c led to a significant reduction in the risk of developing DR (hazard ratio, 0.73 per 1% HbA1c decrement; 95% confidence interval, 0.58 to 0.91; P=0.005). Conclusion This prospective cohort study demonstrates that glycemic control, diabetes duration, age, and albuminuria are important risk factors for the development of DR. More aggressive retinal screening for T2DM patients diagnosed with DR should be required in order to not miss rapid progression of DR.

The association between abnormal heart rate variability and new onset of chronic kidney disease in patients with type 2 diabetes: A ten-year follow-up study

AIMS We investigated the association between cardiovascular autonomic neuropathy (CAN) and the future development of chronic kidney disease (CKD) in patients with type 2 diabetes. METHODS From Jan 2003 to Dec 2004, 1117 patients with type 2 diabetes without CKD (estimated glomerular filtration rate [eGFR] ≥ 60 ml/min/1.73 m(2)), aged 25-75 years, were consecutively enrolled. A cardiovascular autonomic function test (AFT) was performed using heart rate variability parameters. The eGFR was measured at least more than once every year, and new onset CKD was defined as eGFR < 60 ml/min/1.73 m(2) using a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS Among the 755 (67.6%) patients who completed the follow-up evaluation for 9.6 years, 272 patients (36.0%) showed a CKD stage ≥3. The patients who developed CKD were older, had a longer duration of diabetes, had hypertension, received more insulin and ACE inhibitor/angiotensin receptor blocker (ARB) treatment, and exhibited lower baseline eGFR, HbA1c, and albuminuria levels. Compared to patients without CKD, more patients with CKD at follow-up had CAN at baseline. In a multivariate analysis, after adjustment for age, sex, diabetes duration, presence of hypertension, mean HbA1c, diabetic complications, use of insulin, ACE inhibitor/ARB, statin, and baseline eGFR, the development of CKD was significantly associated with the presence of CAN (HR 2.62, 95% CI 1.87-3.67, P<0.001). CONCLUSIONS In this prospective, longitudinal, observational cohort study, we demonstrated that diabetic CAN was an independent prognostic factor for the future development of CKD in type 2 diabetes.

Cardiovascular Autonomic Dysfunction Predicts Diabetic Foot Ulcers in Patients With Type 2 Diabetes Without Diabetic Polyneuropathy.

AbstractWe investigated the factors that might influence the development of diabetic foot ulcers (DFUs) in type 2 diabetes patients without diabetic polyneuropathy (DPN).From January 2000 to December 2005, a total of 595 patients who had type 2 diabetes without DPN between the ages of 25 and 75 years, and had no prior history of DFUs were consecutively enrolled in the study. A cardiovascular autonomic function test was performed to diagnose cardiovascular autonomic neuropathy (CAN) using heart rate variability parameters.The median follow-up time was 13.3 years. Among the 449 (75.4%) patients who completed the follow-up evaluation, 22 (4.9%) patients developed new ulcers, and 6 (1.3%) patients underwent the procedure for lower extremity amputations. The patients in the DFUs group had a longer duration of diabetes, higher baseline HbA1c levels, higher rates of nephropathy, and CAN. A Cox hazard regression analysis results revealed that the development of DFUs was significantly associated with the presence of CAN (normal vs definite CAN; HR, 4.45; 95% confidence interval, 1.29–15.33) after adjusting for possible confounding factors.The development of DFUs was independently associated with CAN in patients with type 2 diabetes without DPN. We suggested the importance of CAN as a predictor of DFUs even in the patients without DPN, and the need to pay attention to patients with definite CAN and type 2 diabetes.

Diabetic Cardiovascular Autonomic Neuropathy Predicts Recurrent Cardiovascular Diseases in Patients with Type 2 Diabetes

Cardiovascular autonomic neuropathy (CAN) is a risk factor for cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. This study evaluated the relationship between CAN and recurrent CVD in type 2 diabetes. A total of 206 patients with type 2 diabetes who had a history of CVD within 3 years of enrollment were consecutively recruited from January 2001 to December 2009 and followed-up until December 2015. Cardiovascular autonomic function tests were performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to Valsalva maneuver and standing. We estimated the recurrence of CVD events during the follow-up period. A total of 159 (77.2%) of the 206 patients enrolled completed the follow up, and 78 (49.1%) patients had recurrent episodes of CVD, with an incidence rate of 75.6 per 1,000 patient-years. The mean age and diabetes duration were 62.5 ± 8.7 and 9.2 ± 6.9 years, respectively. Patients who developed recurrent CVD also exhibited hypertension (P = 0.004), diabetic nephropathy (P = 0.012), higher mean systolic blood pressure (P = 0.006), urinary albumin excretion (P = 0.015), and mean triglyceride level (P = 0.035) than did patients without recurrent CVD. Multivariable Cox hazard regression analysis revealed that definite CAN was significantly associated with an increased risk of recurrent CVD (hazard ratio [HR] 3.03; 95% confidence interval [CI] 1.39−6.60; P = 0.005). Definite CAN was an independent predictor for recurrent CVD in patients with type 2 diabetes who had a known prior CVD event.

Lipoprotein(a) predicts the development of diabetic retinopathy in people with type 2 diabetes mellitus

BACKGROUND Lipoprotein(a) [Lp(a)] has mainly been considered to be a predictor of the incidence of cardiovascular disease. In addition, previous studies have shown potential linkage between Lp(a) and diabetic microvascular complications. OBJECTIVES We investigated the incidence and risk factors for the development of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS A total of 787 patients with type 2 diabetes without DR were consecutively enrolled and followed up prospectively. Retinopathy evaluation was annually performed by ophthalmologists. The main outcome was new onset of DR. RESULTS The median follow-up time was 11.1 years. Patients in the DR group had a longer duration of diabetes (P < .001), higher baseline HbA1c (P < .001), higher albuminuria level (P = .033), and higher level of Lp(a) (P = .005). After adjusting for sex, age, diabetes duration, presence of hypertension, renal function, LDL cholesterol, mean HbA1c, and medications, the development of DR was significantly associated with the serum Lp(a) level (HR 1.57, 95% confidence interval [1.11-2.24]; P = .012, comparing the 4th vs 1st quartile of Lp(a)). The patient group with the highest quartile range of Lp(a) and mean HbA1c levels ≥7.0% had an HR of 5.09 (95% confidence interval [2.63-9.84]; P < .001) for developing DR compared with patients with lower levels of both factors. CONCLUSIONS In this prospective cohort study, we demonstrated that the DR was independently associated with the serum Lp(a) level in patients with type 2 diabetes.

Lipoprotein(a) predicts a new onset of chronic kidney disease in people with Type 2 diabetes mellitus.

We investigated the association between lipoprotein(a) [Lp(a)] level and new‐onset chronic kidney disease (CKD) in patients with Type 2 diabetes.

Risk Factors and Adverse Outcomes of Severe Hypoglycemia in Type 2 Diabetes Mellitus

Hypoglycemia has been considered as a major barrier to achieving the proper glycemic target in type 2 diabetes mellitus patients. In particular, severe hypoglycemia (SH), which is defined as a hypoglycemic episode requiring the assistance of another person to raise the patients glucose level, is a serious complication of diabetes because of its possible fatal outcomes. Recently, the recommendations for diabetes care have emphasized a patient-centered approach, considering the individualized patient factors including hypoglycemia. Many studies have been performed which analyzed the risk factors and clinical outcomes for SH. From the studies, researchers recommend that targeting a less stringent glycosylated hemoglobin level and selecting a safer class of drugs for hypoglycemia are appropriate for patients with a high risk of SH. Also, careful clinical attention to prevent hypoglycemia, including intensive education, is necessary to minimize the risk of SH and SH-related fatal outcomes.