Structural Gray and White Matter Differences in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia

Abstract Context Type 1 diabetes (T1D) is associated with an increased risk of cognitive decline, where severe hypoglycemia (SH) and impaired awareness of hypoglycemia (IAH) may play a role. While there is evidence of a possible association between IAH and brain damage, the potential brain changes remain poorly characterized by magnetic resonance imaging (MRI). Objective To investigate whether there are structural brain differences in a group of T1D patients with IAH compared with normal awareness of hypoglycemia (NAH). Design General practice, population-based, cross-sectional study (July 2018 to July 2019). Setting Endocrinology Department, Hospital Santa Creu i Sant Pau. Participants A total of 40 T1D patients (20 each with IAH and NAH) matched for age, sex, T1D duration, and education level. Main Outcome Measures Using different neuroimaging techniques, we compared whole-brain gray matter (GM) and white matter (WM) differences. We used voxel-based morphometry and cortical surface area analysis methods to assess GM differences, and fractional anisotropy (FA) to assess WM differences. Results Compared with patients with T1D-NAH, patients with T1D-IAH had reduced GM volumes and cortical surface areas, especially in frontal and parietal regions (P < 0.05 corrected), and also showed reduced FA values in major WM tracts. The observed MRI differences correlated with both SH frequency and IAH severity. Conclusions MRI for patients with T1D show that IAH is associated with brain changes involving both GM and WM. Further research is needed to elucidate whether the observed differences are a consequence of increased SH episode frequency and increased IAH severity.

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Predictors of Recurrent Severe Hypoglycemia in Adults With Type 1 Diabetes and Impaired Awareness of Hypoglycemia During the HypoCOMPaSS Study

Diabetes Care ◽

10.2337/dc19-0630 ◽

2019 ◽

Vol 43 (1) ◽

pp. 44-52 ◽

Cited By ~ 4

Author(s):

Anneliese J.S. Flatt ◽

Stuart A. Little ◽

Jane Speight ◽

Lalantha Leelarathna ◽

Emma Walkinshaw ◽

...

Keyword(s):

Type 1 Diabetes ◽

Severe Hypoglycemia ◽

Impaired Awareness

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Prevalence of bone fracture and its association with severe hypoglycemia in Japanese patients with type 1 diabetes

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-002099 ◽

2021 ◽

Vol 9 (1) ◽

pp. e002099

Author(s):

Yuji Komorita ◽

Masae Minami ◽

Yasutaka Maeda ◽

Rie Yoshioka ◽

Toshiaki Ohkuma ◽

...

Keyword(s):

Risk Factors ◽

Type 1 Diabetes ◽

Fracture Risk ◽

Bone Fracture ◽

Severe Hypoglycemia ◽

Japanese Patients ◽

Anatomic Site ◽

Cross Sectional ◽

History Of

IntroductionType 1 diabetes (T1D) is associated with higher fracture risk. However, few studies have investigated the relationship between severe hypoglycemia and fracture risk in patients with T1D, and the results are controversial. Besides, none has investigated the risk factors for fracture in Asian patients with T1D. The aim of the present study was to investigate the prevalence of bone fracture and its relationship between severe hypoglycemia and other risk factors in Japanese patients with T1D.Research design and methodsThe single-center cross-sectional study enrolled 388 Japanese patients with T1D (mean age, 45.2 years; women, 60.4%; mean duration of diabetes, 16.6 years) between October 2019 and April 2020. The occurrence and circumstances of any fracture after the diagnosis of T1D were identified using a self-administered questionnaire. The main outcomes were any anatomic site of fracture and fall-related fracture. Severe hypoglycemia was defined as an episode of hypoglycemia that required the assistance of others to achieve recovery.ResultsA total of 92 fractures occurred in 64 patients, and 59 fractures (64%) were fall-related. Only one participant experienced fracture within the 10 years following their diagnosis of diabetes. In logistic regression analysis, the multivariate-adjusted ORs (95% CIs) of a history of severe hypoglycemia were 2.11 (1.11 to 4.09) for any fracture and 1.91 (0.93 to 4.02) for fall-related fracture. Fourteen of 18 participants with multiple episodes of any type of fracture had a history of severe hypoglycemia (p<0.001 vs no fracture).ConclusionsWe have shown that a history of severe hypoglycemia is significantly associated with a higher risk of bone fracture in Japanese patients with T1D.

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Low levels of soluble TWEAK, indicating on-going inflammation, were associated with depression in type 1 diabetes: a cross-sectional study

BMC Psychiatry ◽

10.1186/s12888-020-02977-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Eva O. Melin ◽

Jonatan Dereke ◽

Magnus Hillman

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Goodness Of Fit ◽

Hdl Cholesterol ◽

Cross Sectional ◽

Cholesterol Levels ◽

Increased Risk ◽

Galectin 3 ◽

Low Levels

Abstract Background Low levels of the soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) and depression are linked to cardiovascular disease. Galectin-3, inadequate glycemic control and low high-density lipoprotein (HDL)-cholesterol levels were previously linked to depression in these patients with type 1 diabetes mellitus (T1DM). The main aim was to explore whether sTWEAK was associated with depression. A secondary aim was to explore diabetes related variables associated with low sTWEAK. Methods Cross-sectional design. T1DM patients (n = 283, men 56%, age18–59 years) were consecutively recruited from one specialist diabetes clinic. Depression was defined as Hospital Anxiety and Depression Scale-Depression sub scale ≥8 points. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. Enzyme linked immunosorbent assays were used to measure sTWEAK and galectin-3. Low sTWEAK was defined as < 7.2 ng/ml and high galectin-3 as ≥2.6 ng/ml. Multiple logistic regression analyses were performed, calibrated and validated for goodness of fit. We adjusted for age, sex, diabetes duration, galectin-3, metabolic variables, serum-creatinine, smoking, physical inactivity, medication, and cardiovascular complications. Results For 29 depressed versus 254 non-depressed patients the prevalence rates were for low sTWEAK: 93 and 68% (p = 0.003) and for high galectin-3: 34 and 13% (p = 0.005) respectively. HDL-cholesterol levels were lower for the depressed (p = 0.015). Patients with low sTWEAK versus high sTWEAK had lower usage of continuous subcutaneous insulin infusion (CSII) (6% versus 17%, p = 0.005). Low sTWEAK (adjusted odds ratio (AOR) 9.0, p = 0.006), high galectin-3 (AOR 6.3, p = 0.001), HDL-cholesterol (per mmol/l) (AOR 0.1, p = 0.006), use of antidepressants (AOR 8.4, p < 0.001), and age (per year) (AOR 1.05, p = 0.027) were associated with depression. CSII (AOR 0.3, p = 0.003) and depression (AOR 7.1, p = 0.009) were associated with low sTWEAK. Conclusions Lower levels of sTWEAK and HDL-cholesterol and higher levels of galectin-3 were independently associated with depression in T1DM. These factors might all contribute to the increased risk for cardiovascular disease and mortality previously demonstrated in patients with depression. CSII (inversely) and depression were independently associated with low sTWEAK levels.

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Association of glycemic variability and hypoglycemia with distal symmetrical polyneuropathy in adults with type 1 diabetes

Scientific Reports ◽

10.1038/s41598-021-02258-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ziyang Shen ◽

Hemin Jiang ◽

Rong Huang ◽

Yunting Zhou ◽

Qian Li ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glycemic Variability ◽

Mean Amplitude ◽

Cross Sectional Study ◽

Cross Sectional ◽

C Peptide ◽

Nocturnal Hypoglycemia ◽

Increased Risk ◽

Distal Symmetrical Polyneuropathy

AbstractPrevious studies exploring the influence of glycemic variability (GV) on the pathogenesis of distal symmetrical polyneuropathy (DSPN) in type 1 diabetes (T1DM) produced conflicting results. The aim of this study was to assess the relationship between GV and DSPN in T1DM. Adults with T1DM were included in this cross-sectional study and asked to undergo 3-day CGM. GV quantified by coefficient of variation (CV) and mean amplitude of glucose excursions (MAGE) were obtained from CGM. Clinical characteristics and biochemical assessments were collected for analysis. The study comprised 152 T1DM patients (53.9% males) with mean age of 44.2 year. Higher levels of age and duration of diabetes and lower levels of total cholesterol, LDL, fasting C-peptide and postprandial C-peptide were observed in DSPN subjects. DSPN groups displayed a higher blood glucose between 00:00 and 12:59 according to the CGM profile. Higher MAGE and CV were associated with increased risk of DSPN in the fully adjusted model. Meanwhile, a significant association between measurements of hypoglycemia, especially nocturnal hypoglycemia, and DSPN was found after multiple tests. CGM parameters describing the glycemic variability and hypoglycemia were potential risk factors for DSPN in adults with T1DM.

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Maternal and child gluten intake and risk of type 1 diabetes: The Norwegian Mother and Child Cohort Study

10.1101/19001883 ◽

2019 ◽

Author(s):

Nicolai A Lund-Blix ◽

German Tapia ◽

Karl Mårild ◽

Anne Lise Brantsaeter ◽

Pål R Njølstad ◽

...

Keyword(s):

Type 1 Diabetes ◽

Cohort Study ◽

Confidence Interval ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Pregnancy Cohort ◽

Increased Risk ◽

Mother And Child

ABSTRACTOBJECTIVETo examine the association between maternal and child gluten intake and risk of type 1 diabetes in children.DESIGNPregnancy cohortSETTINGPopulation-based, nation-wide study in NorwayPARTICIPANTS86,306 children in The Norwegian Mother and Child Cohort Study born from 1999 through 2009, followed to April 15, 2018.MAIN OUTCOME MEASURESClinical type 1 diabetes, ascertained in a nation-wide childhood diabetes registry. Hazard ratios were estimated using Cox regression for the exposures maternal gluten intake up to week 22 of pregnancy and child’s gluten intake when the child was 18 months old.RESULTSDuring a mean follow-up of 12.3 years (range 0.7-16.0), 346 children (0.4%) developed type 1 diabetes (incidence rate 32.6 per 100,000 person-years). The average gluten intake was 13.6 grams/day for mothers during pregnancy, and 8.8 grams/day for the child at 18 months of age. Maternal gluten intake in mid-pregnancy was not associated with the development of type 1 diabetes in the child (adjusted hazard ratio 1.02 (95% confidence interval 0.73 to 1.43) per 10 grams/day increase in gluten intake). However, the child’s gluten intake at 18 months of age was associated with an increased risk of later developing type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake).CONCLUSIONSThis study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the risk of type 1 diabetes in the child.WHAT IS ALREADY KNOWN ON THIS TOPICA national prospective cohort study from Denmark found that a high maternal gluten intake during pregnancy could increase the risk of type 1 diabetes in the offspring (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 grams/day increase in gluten intake). No studies have investigated the relation between the amount of gluten intake by both the mother during pregnancy and the child in early life and risk of developing type 1 diabetes in childhood.WHAT THIS STUDY ADDSIn this prospective population-based pregnancy cohort with 86,306 children of whom 346 developed type 1 diabetes we found that the child’s gluten intake at 18 months of age was associated with the risk of type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake). This study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the child’s risk of type 1 diabetes.

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