Peptide receptor radionuclide therapy as a tool for the treatment of severe hypoglycemia in patients with primary inoperable insulinoma

Objectives Severe hypoglycemia in a course of inoperable insulinoma may be life-threating and often it is not well controlled, even by high doses of diazoxide requiring second line treatment. Among available methods PRRT is characterized by relatively low toxicity and is connected with favorable antitumor effect. The aim of the study was an evaluation of the PRRT effectiveness in control of hypoglycemia in patients with primary inoperable insulinoma. Methods Three patients (female with metastatic insulinoma, male with primary inoperable pancreatic tumor, female with MEN1 syndrome and hepatic metastases) were treated with PRRT due to severe hypoglycemia poorly controlled by diazoxide in course of primary inoperable insulinoma. Results Patient 1 baseline fasting glucose concentration increased from 2.4 mmol/L [3.30–5.60] to 5.9 mmol/L after PRRT. In patient 2 fasting glucose level 2.30 mmol/L increased after PRRT to 7.0 mmol/L, while baseline insulin level initially 31.15 uU/mL [2.6–24.9] decreased to 15.4 uU/mL. In patients 3, baseline fasting glucose level 2.5 mmol/L increased after PRRT to 7.9 mmol/L, and insulin decreased from 57.9 uU/mL to 6.3 uU/mL. In imaging there was partial response (PR) in patient 1 and 2 and stabilization of the tumor size in patient 3. In patient 2 reduction of tumor infiltration let for curative surgery performed 4 months after PPRT. Conclusions PRRT may be effective as a first or second line treatment in management of hypoglycemia for patients with hormonally active inoperable insulinoma.

Oral health and longitudinal changes in fasting glucose levels: A nationwide cohort study

We investigated the association between oral hygiene indicators of periodontitis, tooth loss, and tooth brushing on the longitudinal fasting glucose level in non-diabetic subjects. Using a nationwide health screening database in Korea, we included non-diabetic individuals who received a health screening program with oral health check in 2009–2010. We constructed a linear mixed model for the longitudinal data of fasting glucose from the baseline to 2015. During the 4.84-year of median follow-up, 91,963 individuals (mean age 56.2 at baseline) underwent 392,780 health examinations with fasting glucose level (mmol/L). The presence of periodontitis was 39.3%. In the multivariate linear mixed analysis, periodontitis was related with increased fasting glucose levels (β = 0.0084, standard error = 0.0035, p = 0.018). Similarly, tooth loss was associated with increased level of fasting glucose (β = 0.0246, standard error = 0.0038, p < 0.001). Compared with tooth brushing ≤2 times/day, tooth brushing ≥3 times/day was associated with decreased fasting glucose levels (β = -0.0207, standard error = 0.0033, p < 0.001). Our data showed that periodontitis and tooth loss were associated with increased fasting glucose levels in non-diabetic individuals. The study findings imply that frequent tooth brushing may reduce fasting glucose levels. Further research is needed to determine the effect of periodontal intervention on glycemic control.

Relationship between spectral indicators of heart rate variability and fasting glucose level in healthy persons and elderly patients with discirculatory atherosclerotic encephalopathy

Objective — to establish the peculiarities and relationship of spectral indicators of heart rate variability (HRV), fasting glucose level and lipid profile indicators in practically healthy persons and in elderly patients with dyscirculatory atherosclerotic encephalopathy (DEP). Materials and methods. The study involved 77 subjects of various age, who were divided into two groups: group 1 consisted of apparently healthy persons (19 subjects of middle age and 27 elderly subjects) and group 2 that included patients with DAP manifestations (15 subjects of middle age and 16 elderly persons). In the groups of elderly persons, the subgroups were extracted based on the fasting glucose levels: lower than 6.1 mmol/l and 6.1 mmol/l. The measurements of systolic and diastolic blood pressure were performed in a sitting position after at least 10 min of rest. Plasma glucose levels were determined by a standard glucoseoxidase method, lipid profile was determined by using the automatic analyzer. To assess the risk of cardiovascular disease development, calculations were performed for the indices of the cardiovascular risk: Castelli index and Boizel index. All patients with DEP manifestations underwent 24‑hour Holter ECG monitoring, and healthy people underwent 5 min ECG. Results. The incidence of fasting hyperglycemia in patients with 1 — 2 stage DEP manifestations was in 3.4 times higher (p < 0.05) vs healthy subjects of the same age. The significant correlation has been reveled between age and HDL‑C (r = 0.47, р < 0.05), atherogenic index (r = –0.40, р < 0.05), heart rate (r = –0.45, р < 0.05), Castelli index (r = –0.40, р < 0.05), Boizel index (r = –0.31, р < 0.05), heart rate (r = –0.45, р < 0.05). Moreover, correlation has been established between Boizel index and heart rate (r = +0.44, р < 0.05), heart rate and LF/HF (r = +0.57, р < 0.05), between TG and heart rate (r = +0.43, р < 0.05), LF/HF (r = +0.53, р < 0.05) and between levels of very low density lipoprotein cholesterol and heart rate (r = +0.44 р < 0.05), LF/HF (r = +0.53, р < 0. 05). It has been established that hyperglycemia and dyslipidemia significantly affected spectral heart rate variability indices in patients with encephalopathy manifestations. Conclusions. With ageing, the frequency of fasting hyperglycemia in patients with 1 — 2 stage DEP manifestations was significantly higher in 3.4 times in comparison with practically healthy individuals of the same age. In the group of practically healthy persons over 60 years old, the tendency has been revealed towards a decrease in the spectral parameters of HRV LF and HF, which indicates HRV decrease. With the development of 1 — 2 stages DEP, even in the middle age, a significant decrease in the value of HF (parasympathetic influence) and a significant increase in the value of LF (sympathetic activity) were revealed. In elderly people with signs of 1 — 2 stage DEP with normoglycemia and fasting hyperglycemia against the background of dyslipidemia, the sympathetic link of the autonomic nervous system is activated, accompanied by an increase in the index of vascular complications. In patients with 1 — 2 stages DEP and fasting hyperglycemia, this tendency was even more pronounced. This fact can serve as confirmation that in the development of pre‑diabetic disorders (fasting hyperglycemia) one of the pathogenic mechanisms is the violation of the central regulatory mechanisms, which in turn leads to the violation of the autonomic balance with the prevalence of sympathicotonia, and a decrease in the parasympathetic effect on the heart, which leads to development of autonomous cardiac neuropathy.

Different Curve Shapes of Fasting Glucose and Various Obesity-Related Indices by Diabetes and Sex

Fasting plasma glucose (FPG) and obesity-related indices are prognostic factors for adverse outcomes in both subjects with and without diabetes. A few studies have investigated sex differences in obesity indices related to the risk of diabetes, however no studies have compared the relationship between FPG and obesity-related indices by diabetes and sex. Therefore, in this study, we compared the curve shapes of FPG and various obesity-related indices by diabetes, and further explored sex differences in these associations. Data were derived from the Taiwan Biobank database, which included 5000 registered individuals. We used an adjusted generalized linear regression model and calculated the difference of least square means (Lsmean; standard error, SE) for males and females with and without diabetes. Associations between obesity-related indices and fasting glucose level by diabetes and sex groups were estimated, and the ORTHOREG procedure was used to construct B-splines. The post-fitting for linear models procedure was used to determine the range at which the trends separated significantly. The diabetes/sex/FPG interaction term was significant for all obesity-related indices, including body mass index, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, lipid accumulation product, body roundness index, conicity index, body adiposity index and abdominal volume index. B-spline comparisons between males and females did not reach significance. However, FPG affected the trend towards obesity-related indices. As the fasting glucose level increased, the values of obesity-related indices varied more obviously in the participants without diabetes than in those with diabetes mellitus. The current study revealed that there was a different relationship between FPG and obesity-related indices by diabetes and sex. FPG affected the trend towards obesity-related indices more obviously in participants without diabetes than in those with diabetes. Further studies with a longitudinal design would provide a better understanding of the underlying mechanisms for the relationships.

Analyses of Increased Mortality in New and Known Diabetes in Patients with Coronary Disease Enrolled in the NORSTENT Randomized Study

Background: NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention with drug-eluting stents (DES) or bare-metal stents (BMS) with a 5-year follow-up. Among the patients, 5,512 had measured either fasting glucose level or percent glycated hemoglobin (HbA1c) at the index procedure. That cohort constitutes the present study population analyzing mortality and evaluating treatment heterogeneity of randomized stent in diabetic versus nondiabetic subgroups. Results: The cohort consisted of 4,174 (75.7%) patients without diabetes, 716 (13.0%) with known diabetes, and 622 (11.3%) with no diabetes in history but elevated fasting glucose level >7.0 mmol/L or HbA1c >6.5% and therefore defined as new diabetes. Patients with known diabetes had a significantly increased all-cause (hazard ratio [HR] 1.99, 95% CI 1.51–2.62, p < 0.001), cardiac (subhazard ratio [SHR] 2.47, 95% CI 1.55–3.93, p < 0.001), and noncardiac (SHR 1.74, 95% CI 1.23–2.44, p = 0.002) mortality after adjustment for baseline variables. In the follow-up of 5 years, patients with new diabetes, however, had a marginally increased all-cause (HR 1.40, 95% CI 1.01–1.93, p = 0.043) and significantly increased noncardiac mortality (SHR 1.52, 95% CI 1.06–2.20, p = 0.025), but no increase in cardiac mortality (SHR 1.06, 95% CI 0.53–2.12, p = 0.86) after the same adjustment. The majority of the mortality was cardiac in the first 1–2 years after intervention; thereafter, noncardiac mortality dominated. However, the time period for when noncardiac mortality became the dominating cause varied considerably and significantly between the groups. There was no heterogeneity in mortality in response to randomized stent between diabetics and nondiabetics. Conclusion: Known diabetes has increased cardiac and noncardiac mortality in contrast to new diabetes which is only associated with increased noncardiac mortality during the 5-year follow-up. Diabetic and nondiabetic patients have the same response to the treatment with BMS or DES.

Secondhand Smoke Exposure, Diabetes, Elevated Glucose Level Are Risk Factors for Uterine Cervical Cancer: A Cross-Sectional Study From the Korea National Health and Nutrition Examination Survey (2010-2018)

Background: Human papilloma virus infection and tobacco smoking are the major risk factors for cervical cancer. There are limited studies searching other risk factors for cervical cancer and the results are not consistent. This study investigated the relations between cervical cancer and possible risk factors, including secondhand cigarette smoke exposure, diabetes, work schedule. Methods: In this cross-sectional study, 29,557 women completed a cervical cancer questionnaire and were selected using 2010–2018 data from the Korea National Health and Nutrition Examination Survey. Details in secondhand smoke exposure, diabetes, work schedule were assessed from participants’ health interviews and blood test results were used for fasting glucose level and hemoglobin A1c (HbA1c) level.Results: Two hundred sixty-two women (0.89%) in the sample were diagnosed with cervical cancer. Domestic secondhand smoke exposure, diabetes, high fasting glucose level, and high HbA1c significantly increased cervical cancer risk. The respective odd ratios and 95% confidence intervals were: 1.488 (1.002–2.207), 2.369 (1.713–3.274), 1.008 (1.005–1.009), and 1.304 (1.193–1.425). Weekly work hours and work schedule were not significantly related to cervical cancer incidence.Conclusion: Among Korean women, passive exposure to cigarette smoke at home, diabetes, elevated fasting glucose level, and high HbA1c level all increase risk for cervical cancer.

Association of impaired fasting glucose and Type 2 Diabetes Mellitus with brain volume changes in Alzheimer’s Disease patients analyzed by MRI: a retrospective study

Objectives Alzheimer’s disease (AD), impaired fasting glucose (IFG), and Type 2 diabetes mellitus (T2DM) were reported associated with smaller brain volumes. Nevertheless, the association of hyperglycemia with brain volume changes in AD patients remains unclear. To investigate this issue, structural magnetic resonance imaging was used to compare brain volumes among AD patients with different fasting glucose levels. Methods Eighty-five AD patients were divided into three groups based on their fasting glucose level as suggested by the American Diabetes Association: normal fasting glucose group (AD_NFG, n = 45), AD_IFG group (n = 15), and AD_T2DM group (n = 25). Sagittal 3D T1-weighted images were obtained to calculate the brain volume. Brain parenchyma and 33 brain structures were automatically segmented. Each regional volume was analyzed among groups. For regions with statistical significance, partial correlation analysis was used to evaluate their relationships with fasting glucose level, corrected for Mini-Mental State Examination score, age, education level, cholesterol, triglyceride, and blood pressure. Results Compared with the AD_IFG and AD_NFG groups, the volume of pons in AD_T2DM group was significantly smaller. Fasting glucose was negatively correlated with pontine volume. Conclusions T2DM may exacerbate pontine atrophy in AD patients, and fasting glucose level is associated with pontine volume.