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There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis.
We analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent coronary computed tomographic angiography (CCTA) (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (
Compared with normal individuals, there were no statistically significant differences in the risk of for any atherosclerotic plaque (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.98 to 1.38;
Asymptomatic uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events.
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Obesity has become a common healthcare problem worldwide. Cilia are tiny hair-like organelles on the cell surface that are generated and anchored by the basal body. Non-motile primary cilia have been considered to be evolutionary rudiments until a few decades, but they are now considered as important signaling organelles because many receptors, channels, and signaling molecules are highly expressed in primary cilia. A potential role of primary cilia in metabolic regulation and body weight maintenance has been suspected based on rare genetic disorders termed as ciliopathy, such as Bardet-Biedl syndrome and Alström syndrome, which manifest as obesity. Recent studies have demonstrated involvement of cilia-related cellular signaling pathways in transducing metabolic information in hypothalamic neurons and in determining cellular fate during adipose tissue development. In this review, we summarize the current knowledge about cilia and cilia-associated signaling pathways in the regulation of body metabolism.
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This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin.
This multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea.
Eighty-two Korean patients received ipragliflozin (
Ipragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups.
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SGLT2 Inhibitors as Add-On Therapy to Metformin for People with Type 2 Diabetes: A Review of Placebo-Controlled Trials in Asian versus Non-Asian Patients
Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare.
To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.
Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis.
The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.
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Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description
The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic β-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation.
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Fibroblast growth factor 21 (FGF21) was originally identified as a paroxysm proliferator activated receptor-α target gene product and is a hormone involved in metabolic regulation. The purpose of this study was to investigate the diurnal variation of serum FGF21 concentration in obese and non-obese healthy volunteers.
Blood samples were collected from five non-obese (body mass index [BMI] ≤23 kg/m2) and five obese (BMI ≥25 kg/m2) healthy young men every 30 to 60 minutes over 24 hours. Serum FGF21 concentrations were determined by radioimmunoassay. Anthropometric parameters, glucose, free fatty acid, insulin, leptin, and cortisol concentrations were also measured.
The serum FGF21 concentrations displayed various individual oscillation patterns. The oscillation frequency ranged between 6 and 12 times per day. The average duration of oscillation was 2.52 hours (range, 1.9 to 3.0 hours). The peaks and troughs of FGF21 oscillation showed no circadian rhythm. However, the oscillation frequency had a diurnal variation and was lower during the light-off period than during the light-on period (2.4 vs. 7.3 times,
Various oscillation patterns in serum FGF21 concentration were observed, and reduced oscillation frequencies were seen during sleep. The oscillation patterns of serum FGF21 concentration suggest that FGF21 may be secreted into systemic circulation in a pulsatile manner. Obesity appeared to affect the amplitude of oscillations of serum FGF21.
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Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. Diabetes is known to increase the risk of PAD two- to four-fold. The prevalence of PAD in Korean diabetic patients has not been established. In this study, we investigated the prevalence of PAD in Korean patients with type 2 diabetes attending a large university hospital and analyzed the factors associated with PAD.
A total of 2,002 patients with type 2 diabetes who underwent ankle-brachial index (ABI) measurement in an outpatient clinic were enrolled. PAD was defined as an ABI ≤0.9. Clinical characteristics of 64 patients with PAD were compared with those of 192 age- and sex-matched control patients without PAD.
Of the 2,002 type 2 diabetic patients, 64 (3.2%) were diagnosed as having PAD. PAD was associated with higher prevalences of retinopathy, nephropathy, neuropathy, cerebrovascular and coronary artery disease. Patients with PAD had higher systolic blood pressure and serum triglyceride level and reported higher pack-years of smoking. Multivariate analysis showed that the presence of micro- and macrovascular complications and high systolic blood pressure are factors independently associated with PAD.
The prevalence of PAD in diabetic patients was 3.2%, suggesting that the prevalence in Korean diabetic patients is lower than that of patients in Western countries.
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Kidney function is critical in homocysteine clearance, and plasma homocysteine level is frequently increased in patients with renal failure. On the other hand, recent studies in animals have shown that hyperhomocysteinemia induces renal injury. In this study, we determined whether hyperhomocysteinemia can be a risk factor for the development of microalbuminuria in patients with type 2 diabetes.
A nested case-control study. Of 887 patients with type 2 diabetes who did not have microalbuminuria at baseline, 76 developed microalbuminuria during follow-up (mean, 36.0 ± 11.7 months; range, 18 to 76 months). The control group consisted of 152 age- and sex-matched subjects who did not develop microalbuminuria. Baseline plasma homocysteine concentrations were measured in stored samples.
Baseline plasma homocysteine concentrations and mean HbA1C levels during follow-up were significantly higher in patients who developed microalbuminuria than in those who remained normoalbuminuric. Multivariate logistic regression analysis showed that baseline plasma homocysteine level and mean HbA1C were independent predictors of microalbuminuria in type 2 diabetes.
Hyperhomocysteinemia was associated with increased risk of microalbuminuria in patients with type 2 diabetes supporting the concept that hyperhomocysteinemia has an etiologic role in the pathogenesis of diabetic nephropathy.
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Serum cystatin C level is a more sensitive marker of renal dysfunction than serum creatinine level. Serum cystatin C level was recently reported to predict the development of cardiovascular disease. This study was performed to evaluate whether the cystatin C level is associated with coronary artery disease (CAD), independent of diabetic nephropathy.
We conducted a case-control study to assess the relationship between serum cystatin C level and coronary artery disease in diabetic patients. Among 460 diabetic patients, 38 diabetic patients had CAD. The control group consisted of 38 diabetic patients who were matched to cases by age, sex, and presence/absence of diabetic nephropathy. Serum cystatin C level was measured in stored samples.
Serum cystatin C level was significantly higher in patients with diabetic nephropathy, both in CAD and non-CAD patients. However, serum cystatin C level did not differ between CAD and non-CAD patients, regardless of diabetic nephropathy.
Serum cystatin C level is a marker of renal dysfunction, but not coronary artery disease, in diabetic patients.
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