A case of generalized lipodystrophy-associated progeroid syndrome treated by leptin replacement with short and long-term monitoring of the metabolic and endocrine profiles.

We herein report a case of a 28-year-old man with generalized lipodystrophy-associated progeroid syndrome treated by leptin replacement. He showed symptoms of generalized lipodystrophy around onset of puberty. His body mass index was 11.9 kg/m2, and he had a short stature, birdlike facies, dental crowding due to micrognathia, partial graying and loss of hair, and a high-pitched voice, all of which are typical features of the progeroid syndrome. Laboratory examinations and abdominal ultrasonography revealed diabetes mellitus, insulin-resistance, dyslipidemia, decreased serum leptin levels (2.2 ng/mL), elevated serum hepatobiliary enzyme levels and fatty liver. Whole exome sequencing revealed de novo heterozygous LMNA p.T10I mutation, indicating generalized lipodystrophy-associated progeroid syndrome, which is a newly identified subtype of atypical progeroid syndrome characterized by severe metabolic abnormalities. Daily injection of metreleptin [1.2 mg (0.04 mg/kg)/day] was started. Metreleptin treatment significantly improved his diabetes from HbA1c 11.0% to 5.4% in six months. It also elevated serum testosterone levels. Elevated serum testosterone levels persisted even 1 year after the initiation of metreleptin treatment. To the best of our knowledge, this is the first Japanese case report of generalized lipodystrophy-associated progeroid syndrome. Furthermore, we evaluated short and long-term effectiveness of leptin replacement on generalized lipodystrophy by monitoring metabolic and endocrine profiles.

Late-night salivary cortisol as a screening test for the diagnosis of Cushing's syndrome in Japan.

Measurement of late-night and/or midnight salivary cortisol currently used in US and European countries is a simple and convenient screening test for the initial diagnosis of Cushing's syndrome (CS). Unfortunately, this test has not been widely used in Japan. The purpose of this study was to evaluate the usefulness of the measurement of late-night salivary cortisol as a screening test for the diagnosis of CS in Japan. We studied 27 patients with various causes of CS, consisting of ACTH-dependent Cushing's disease [5] and ectopic ACTH syndrome [4] and ACTH-independent adrenal CS [11] and subclinical CS [7]. Eleven patients with type 2 diabetes and obesity and 16 normal subjects served as control group. Saliva samples were collected at late-night (23:00) in a commercially available device and assayed for cortisol by radioimmunoassay. There were highly significant correlations (P<0.0001) between late-night serum and salivary cortisol levels in normal subjects (r = 0.861) and in patients with CS (r = 0.788). Late-night salivary cortisol levels in CS patients (0.975 +/- 1.56 microg/dl) were significantly higher than those in normal subjects (0.124 +/- 0.031 microg/dl) and in obese diabetic patients (0.146 +/- 0.043 microg/dl), respectively. Twenty-five out of 27 CS patients had late-night salivary cortisol concentrations greater than 0.21 microg/dl, whereas those in control group were less than 0.2 microg/dl. Receiver operating characteristic curve (ROC) analysis showed that the cut-off point of 0.21 microg/dl provides a sensitivity of 93% and a specificity of 100%. Therefore, it is concluded that the measurement of late-night salivary cortisol is an easy and reliable noninvasive screening test for the initial diagnosis of CS, especially useful for large high-risk populations, such as diabetes and obesity.

The number of microvascular complications is associated with an increased risk for severity of periodontitis in type 2 diabetes patients: Results of a multicenter hospital-based cross-sectional study.

AIMS/INTRODUCTION: To explore the relationships between periodontitis and microvascular complications as well as glycemic control in type 2 diabetes patients. MATERIALS AND METHODS: This multicenter, hospital-based, cross-sectional study included 620 patients with type 2 diabetes. We compared the prevalence and severity of periodontitis between patients with ≥1 microvascular complication and those without microvascular complications. We also compared the prevalence and severity of periodontitis among patients with different degrees of glycemic control. RESULTS: After adjusting for confounding factors, multiple logistic regression analysis showed that the severity of periodontitis was significantly associated with the number of microvascular complications (odds ratio 1.3, 95% confidence interval 1.1-1.6), glycated hemoglobin ≥8.0% (64 mmol/mol; odds ratio 1.6; 95% confidence interval 1.1-2.3), and older age (≥50 years; odds ratio 1.7; 95% confidence interval 1.1-2.6). However, the prevalence of periodontitis was not significantly associated with the number of microvascular complications, but was associated with male sex, high glycated hemoglobin (≥8.0% [64 mmol/mol]), older age (≥40 years), longer duration of diabetes (≥15 years) and fewer teeth (≤25). Furthermore, propensity score matching for age, sex, diabetes duration and glycated hemoglobin showed that the incidence of severe periodontitis was significantly higher among patients with microvascular complications than among those without microvascular complications (P < 0.05). CONCLUSIONS: The number of microvascular complications is a risk factor for more severe periodontitis in patients with type 2 diabetes, whereas poor glycemic control is a risk factor for increased prevalence and severity of periodontitis.

Retrograde pyelonephritis and lumbar spondylitis as a result of Salmonella typhi in a type 2 diabetes patient with neurogenic bladder.

We present a case of a 62-year-old diabetic woman with acute pyelonephritis and spondylitis caused by Salmonella typhi. She was admitted to Tokyo Medical Dental University Hospital, Tokyo, Japan, because of unconsciousness and was diagnosed with sepsis by retrograde pyelonephritis as a result of Salmonella typhi. Antibiotics treatment was immediately started; however, she subsequently developed lumbar spondylitis, and long-term conservative treatment with antibiotics and a fixing device were required. This is the first report of a diabetic patient who developed retrograde urinary tract infection with Salmonella typhi, followed by sepsis and spondylitis. The infection could be a result of diabetic neuropathy, presenting neurogenic bladder and hydronephrosis. The patient was successfully treated with antibiotics and became asymptomatic with normal inflammatory marker levels, and no clinical sign of recurrence was observed in the kidney and spine at 4 months.

Periodontal treatment with topical antibiotics improves glycemic control in association with elevated serum adiponectin in patients with type 2 diabetes mellitus.

OBJECTIVES: Chronic inflammation of periodontitis aggravates glycemic control in type 2 diabetic patients through aggravation of insulin resistance. Increased or decreased release of various inflammatory mediators, such as high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and adipokines, such as adiponectin, leptin, and resistin, are presumed to be responsible for developing and progressing insulin resistance. The purpose of this study was to examine the effects of periodontal treatment on glycemic control, serum inflammatory mediators and adipokines in type 2 diabetes patients with periodontitis. METHODS: Twenty-one type 2 diabetic patients with periodontitis received periodontal treatment with topical antibiotics (intervention group) and 8 patients did not receive periodontal treatment (control group). Periodontal examination, including probing pocket depth (PPD) and bleeding on probing (BOP), and blood sampling were performed at baseline, 2 and 6 months after periodontal treatments. Glycated hemoglobin (HbA1c), hs-CRP, TNF-α, IL-6, adiponectin, leptin, and resistin were analyzed. RESULTS: In the intervention group, improvements of PPD and BOP, decrease in HbA1c and elevation of serum adiponectin were observed, while in the control group, all parameters were not changed. Generalized linear model revealed that changes of serum adiponectin and TNF-α and change of BOP correlated significantly with the reduction of HbA1c at 6 months after periodontal treatments. CONCLUSION: The results demonstrated that periodontal treatment improves periodontal status and glycemic control with elevation of serum adiponectin in type 2 diabetic patients. The results suggest that HbA1c is reduced by amelioration of insulin resistance due to elevated serum adiponectin after periodontal treatments.

Improvement of glycemic control after periodontal treatment by resolving gingival inflammation in type 2 diabetic patients with periodontal disease.

UNLABELLED: Aims/Introduction: Chronic inflammation aggravates glycemic control in patients with type 2 diabetes mellitus. An increase or decrease in the release and activities of various inflammatory mediators, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C-reactive protein (CRP), are presumed to be responsible for inducing insulin resistance. The purpose of the present study was to examine the effects of non-surgical periodontal treatment incorporating topical antibiotics on glycemic control and serum inflammatory mediators in patients with type 2 diabetes mellitus with periodontitis. MATERIALS AND METHODS: Periodontal inflammation and periodontal tissue destruction were evaluated by bleeding on probing (BOP) and the probing pocket depth (PPD), respectively. A total of 41 patients with type 2 diabetes and periodontitis received periodontal treatment with the topical application of antibiotics four times within a 2-month period. A periodontal examination, including PPD and BOP, and venous blood sampling were carried out at baseline and at 2 and 6 months after periodontal treatment. Glycated hemoglobin (HbA1c), and serum levels of high-sensitivity (hs)-CRP, TNF-α and IL-6 were analyzed. RESULTS: A generalized linear model showed significant associations between the change in the HbA1c values at 6 months after periodontal treatment, and the change in the BOP, baseline TNF-α levels and the baseline mean PPD. CONCLUSIONS: As BOP is a marker of total gingival inflammation, these results suggest that non-surgical periodontal therapy with topical antibiotics in patients with mild periodontitis might improve glycemic control by resolving periodontal inflammation. Such treatments might be insufficient for the amelioration of insulin resistance in type 2 diabetic patients with severe periodontitis. This trial was registered with the University Hospital Medical Information Network (no. UMIN000006693). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00209.x, 2012).