Predictors for Mild and Severe Hypoglycemia in Insulin-Treated Japanese Diabetic Patients

<div><p>The objective of this study was to explore predictors, including social factors, lifestyle factors, and factors relevant to glycemic control and treatment, for mild and severe hypoglycemia in insulin-treated Japanese diabetic patients. This study included 123 insulin-treated diabetic patients who were referred to the diabetes clinic between January and July 2013 at Shiga University of Medical Science Hospital. After a survey examining the various factors, patients were followed for 6 months. During the follow-up period, blood glucose was self-monitored. Mild hypoglycemia was defined as blood glucose level 50–69 mg/dl, and severe hypoglycemia was defined as blood glucose level ≤49 mg/dl. Multinomial logistic regression was used to estimate the adjusted odds ratio (OR) and 95% confidence interval (CI) of each factor for mild and severe hypoglycemia. During the 6-month follow-up period, 41 (33.3%) patients experienced mild hypoglycemia, and 20 (16.3%) experienced severe hypoglycemia. In multivariable-adjusted analyses, assistance from family members at the time of the insulin injection [presence/absence, OR (95% CI): 0.39 (0.16–0.97)] and drinking [current drinker/non- and ex-drinker, OR (95% CI): 4.89 (1.68–14.25)] affected mild hypoglycemia. Assistance from family members at the time of insulin injection [presence/absence, OR (95% CI): 0.19 (0.05–0.75)] and intensive insulin therapy [yes/no, OR (95% CI): 3.61 (1.06–12.26)] affected severe hypoglycemia. In conclusion, our findings suggest that not only a factor relevant to glycemic control and treatment (intensive insulin therapy) but also a social factor (assistance from family members) and a lifestyle factor (current drinking) were predictors for mild or severe hypoglycemia in Japanese insulin-treated diabetic patients.</p></div

Improved glucose metabolism by <i>Eragrostis tef</i> potentially through beige adipocyte formation and attenuating adipose tissue inflammation

<div><p>Background</p><p>Teff is a staple food in Ethiopia that is rich in dietary fiber. Although gaining popularity in Western countries because it is gluten-free, the effects of teff on glucose metabolism remain unknown.</p><p>Aim</p><p>To evaluate the effects of teff on body weight and glucose metabolism compared with an isocaloric diet containing wheat.</p><p>Results</p><p>Mice fed teff weighed approximately 13% less than mice fed wheat (<i>p</i> < 0.05). The teff-based diet improved glucose tolerance compared with the wheat group with normal chow but not with a high-fat diet. Reduced adipose inflammation characterized by lower expression of <i>TNFα</i>, <i>Mcp1</i>, and <i>CD11c</i>, together with higher levels of cecal short chain fatty acids such as acetate, compared with the control diet containing wheat after 14 weeks of dietary treatment. In addition, beige adipocyte formation, characterized by increased expression of <i>Ucp-1</i> (~7-fold) and <i>Cidea</i> (~3-fold), was observed in the teff groups compared with the wheat group. Moreover, a body-weight matched experiment revealed that teff improved glucose tolerance in a manner independent of body weight reduction after 6 weeks of dietary treatment. Enhanced beige adipocyte formation without improved adipose inflammation in a body-weight matched experiment suggests that the improved glucose metabolism was a consequence of beige adipocyte formation, but not solely through adipose inflammation. However, these differences between teff- and wheat-containing diets were not observed in the high-fat diet group.</p><p>Conclusions</p><p>Teff improved glucose tolerance likely by promoting beige adipocyte formation and improved adipose inflammation.</p></div

Characteristics of 123 Japanese patients with insulin-treated diabetes.

<p>HbA1c, hemoglobin A1c; eGFR, estimated glomerular filtration rate.</p><p>Characteristics of 123 Japanese patients with insulin-treated diabetes.</p

Comparison of body weight and glucose metabolism between mice fed a high-fat diet with wheat (HFD-wheat: Blue) or teff (HFD-teff: Red).

<p>A: Study design. B: Body weight. C: Energy intake. D: Intraperitoneal glucose tolerance test (IPGTT) at week 6 (2 g/kg). E: Blood glucose levels after oral mixed meal administration of each assigned diet (2.2g/kg body weight, 33% solution in dH₂O) after 16 h of fasting at week 6. F: Plasma insulin levels during OMTT. G: Oral glucose tolerance test (OGTT) at week 9 (2 g/kg). H: Insulin concentration during OGTT. I: Intraperitoneal insulin tolerance test (IPITT) at week 9 (0.5 U/kg). * <i>p</i> < 0.05, n.s. = not significant. n = 5–9 in each groups.</p

Comparison of body weight and glucose metabolism between mice fed a chow diet with wheat (CD-wheat: Blue) or teff (CD-teff: Red).

<p>A: Study design. B: Body weight. C: Energy intake. D: Intraperitoneal glucose tolerance test (IPGTT) at week 6 (2.0 g/kg). E: Blood glucose levels after oral mixed meal administration of each assigned diet (2.2g/kg body weight, 33% solution in dH₂O) after 16 h of fasting at week 6. F: Plasma insulin levels during OMTT. G: Oral glucose tolerance test (OGTT) at week 9 (2 g/kg). H: Insulin concentration during OGTT. I: Intraperitoneal insulin tolerance test (IPITT) at week 9 (0.5 U/kg). * <i>p</i> < 0.05, n.s. = not significant. n = 5–9 in each groups.</p

Odds ratios and 95% confidence intervals for mild and severe hypoglycemia according to each factor in 123 patients with insulin-treated diabetes during the 6-month follow-up period.

<p>Multinomial logistic regression was used to estimate the adjusted OR and 95% CI for mild and severe hypoglycemia.</p><p>Response variable: 1 = patients who did not experience hypoglycemia, 2 = patients who experienced only mild hypoglycemia, and 3 = patients who experienced severe hypoglycemia.</p><p>^aAdjusted for age, sex, assistance from family members at the insulin injection (presence or absence), drinking (current drinker or non- and ex-drinker), and intensive insulin therapy (yes or no).</p><p>OR, odds ratio; CI, confidence interval.</p><p>Odds ratios and 95% confidence intervals for mild and severe hypoglycemia according to each factor in 123 patients with insulin-treated diabetes during the 6-month follow-up period.</p

Adipose tissue inflammation in mice fed a chow diet with wheat (CD-wheat) or chow diet with teff (CD-teff) for 14 weeks.

<p>A: Immunostaining of the macrophage marker F4/80 (brown) in adipose tissue (scale bar = 100 μM). B: mRNA levels of the macrophage marker, <i>F4/80</i> and <i>CD11c</i>, tumor necrosis factor α (<i>TNF</i>α), monocyte chemoattractant protein-1 (<i>Mcp-1</i>), Forkhead Boxprotein P3 <i>(Foxp3</i>), and adiponectin in adipose tissue. All mRNA expression data were normalized to <i>36B4</i>. C: Immunofluorescence staining for DAPI (blue), F4/80 (red) and TNFα (green) in adipose tissue (scale bar, 100 μm). * <i>p</i> < 0.05. n.s. = not significant.</p

Composition and energy density of experimental diets.

<p>Composition and energy density of experimental diets.</p

A proposed model of the effects of teff diet on glucose metabolism.

<p>Illustrated is a model of how teff improves glucose tolerance by increasing beige adipocyte formation and inhibiting adipose inflammation through increasing SCFAs concentrations.</p

The possible role of beige adipocyte formation in CD-teff treated mice.

<p>A: mRNA levels of thermogenic and beige adipocyte marker genes in the inguinal adipose tissue from mice fed for 14 weeks with CD-what or CD-teff. All mRNA expression data were normalized to <i>36B4</i>. B: Core body temperatures were measured at 10:00 AM under <i>ad lib</i> feeding conditions. C: Hematoxylin and eosin staining and Ucp-1 immunostaining in iWAT from CD-wheat and CD-teff mice (left and right columns, respectively). D: Immunofluorescence staining of perilipin (green) in iWAT. E: The size and distribution of adipocytes from iWAT pad of CD-wheat and CD-teff mice quantified by ImageJ. F: Number of adipocyte. n = 3. *<i>p</i> < 0.05, ** <i>p</i> < 0.01. n.s. = not significant.</p