People with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Hypoglycemia is a candidate risk factor, but the direction of association between episodes of severe ...hypoglycemia and cognitive decline in type 2 diabetes remains uncertain.
In the Edinburgh Type 2 Diabetes Study, cognitive function was assessed in 831 adults with type 2 diabetes (aged 60-75 years) at baseline and after 4 years. Scores on seven neuropsychological tests were combined into a standardized general ability factor g. Self-reported history of severe hypoglycemia at baseline (history of hypoglycemia) and at follow-up (incident hypoglycemia) was recorded.
A history of hypoglycemia was reported by 9.3% of subjects, and 10.2% reported incident hypoglycemia. Incident hypoglycemia was associated with poorer cognitive ability at baseline (age- and sex-adjusted odds ratio for lowest tertile of g 2.04 95% CI 1.25-3.31, P = 0.004). Both history of hypoglycemia and incident hypoglycemia were also associated with greater cognitive decline during follow-up (mean follow-up g adjusted for age, sex, and baseline g -0.25 vs. 0.03 P = 0.02 and -0.28 vs. 0.04 P = 0.01, respectively), including after addition of vascular risk factors and cardiovascular and microvascular disease to the models (-0.23 vs. 0.03 P = 0.04 and -0.21 vs. 0.05 P = 0.03, respectively).
The relationship between cognitive impairment and hypoglycemia appeared complex, with severe hypoglycemia associated with both poorer initial cognitive ability and accelerated cognitive decline.
The objective of this cross-sectional study was to explore the relationship of detectable C-peptide secretion in type 1 diabetes to clinical features and to the genetic architecture of diabetes.
...C-peptide was measured in an untimed serum sample in the SDRNT1BIO cohort of 6076 Scottish people with clinically diagnosed type 1 diabetes or latent autoimmune diabetes of adulthood. Risk scores at loci previously associated with type 1 and type 2 diabetes were calculated from publicly available summary statistics.
Prevalence of detectable C-peptide varied from 19% in those with onset before age 15 and duration greater than 15 years to 92% in those with onset after age 35 and duration less than 5 years. Twenty-nine percent of variance in C-peptide levels was accounted for by associations with male gender, late age at onset and short duration. The SNP heritability of residual C-peptide secretion adjusted for gender, age at onset and duration was estimated as 26%. Genotypic risk score for type 1 diabetes was inversely associated with detectable C-peptide secretion: the most strongly associated loci were the HLA and INS gene regions. A risk score for type 1 diabetes based on the HLA DR3 and DQ8-DR4 serotypes was strongly associated with early age at onset and inversely associated with C-peptide persistence. For C-peptide but not age at onset, there were strong associations with risk scores for type 1 and type 2 diabetes that were based on SNPs in the HLA region but not accounted for by HLA serotype.
Persistence of C-peptide secretion varies widely in people clinically diagnosed as type 1 diabetes. C-peptide persistence is influenced by variants in the HLA region that are different from those determining risk of early-onset type 1 diabetes. Known risk loci for diabetes account for only a small proportion of the genetic effects on C-peptide persistence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims/hypothesis
Our aim was to determine whether a range of prespecified retinal vessel traits were associated with incident diabetic retinopathy in adults with type 2 diabetes.
Methods
In the ...prospective observational cohort Edinburgh Type 2 Diabetes Study of 1066 adults with type 2 diabetes, aged 60–75 years at recruitment, 718 were free from diabetic retinopathy at baseline. Baseline retinal traits including vessel widths, tortuosity (curvature) and fractal dimensions (network complexity), were quantified using fundus camera images and semiautomated software, and analysed using logistic regression for their association with incident diabetic retinopathy over 10 years.
Results
The incidence of diabetic retinopathy was 11.4% (
n
= 82) over 10 years. After adjustment for a range of vascular and diabetes-related risk factors, both increased venular tortuosity (OR 1.51; 95% CI 1.15, 1.98;
p
= 0.003) and decreased fractal dimension (OR 0.75; 95% CI 0.58, 0.96;
p
= 0.025) were associated with incident retinopathy. There was no evidence of an association with arterial tortuosity, and associations between measurements of vessel widths and retinopathy lost statistical significance after adjustment for diabetes-related factors and vascular disease. Adding venular tortuosity to a model including established risk factors for diabetic retinopathy (HbA
1c
, BP and kidney function) improved the discriminative ability (C statistic increased from 0.624 to 0.640,
p
= 0.013), but no such benefit was found with fractal dimension.
Conclusions/interpretation
Increased retinal venular tortuosity and decreased fractal dimension are associated with incident diabetic retinopathy, independent of classical risk factors. There is some evidence that venular tortuosity may be a useful biomarker to improve the predictive ability of models based on established retinopathy risk factors, and its inclusion in further risk prediction modelling is warranted.
Graphical abstract
To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes.
C-peptide was measured in an untimed blood sample in the Scottish ...Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) cohort of 6,076 people with type 1 diabetes monitored for an average of 5.2 years.
In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 vs. <5 pmol/L were as follows: insulin dose at baseline, 27% lower (
= 2 × 10
); HbA
during follow-up, 4.9 mmol/mol lower (
= 3 × 10
); hazard ratio for hospital admission for diabetic ketoacidosis during follow-up, 0.44 (
= 0.0001); odds ratio for incident retinopathy, 0.51 (
= 0.0003). Effects on the risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/L). In regression models contrasting C-peptide 30 to <200 pmol/L with <5 pmol/L, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (
= 6 × 10
), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (
= 0.03).
These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the Diabetes Control and Complications Trial (DCCT) intensively treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/L. This has obvious implications for the design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes.
Increasing numbers of people are developing type 2 diabetes mellitus, but interventions to prevent and treat the classic microvascular and macrovascular complications have improved, so that people ...are living longer with the condition. This trend means that novel complications of type 2 diabetes mellitus, which are not targeted by current management strategies, could start to emerge. Cognitive impairment and dementia could come into this category. Type 2 diabetes mellitus is associated with a 1.5-2.5-fold increased risk of dementia. The etiology of dementia and cognitive impairment in people with type 2 diabetes mellitus is probably multifactorial. Chronic hyperglycemia is implicated, perhaps by promoting the development of cerebral microvascular disease. Data suggest that the brains of older people with type 2 diabetes mellitus might be vulnerable to the effects of recurrent, severe hypoglycemia. Other possible moderators of cognitive function include inflammatory mediators, rheological factors and dysregulation of the hypothalamic-pituitary-adrenal axis. Cognitive function should now be included as a standard end point in randomized trials of therapeutic interventions in patients with type 2 diabetes mellitus.
Aims/hypothesis
We aimed to assess whether persistence of C-peptide secretion is associated with less glucose variability and fewer low-glucose events in adults with type 1 diabetes who use flash ...monitoring.
Methods
We performed a cross-sectional study of 290 adults attending a university teaching hospital diabetes clinic, with type 1 diabetes, who use flash monitoring and in whom a random plasma C-peptide was available in the past 2 years. Variables relating to flash monitoring were compared between individuals with low C-peptide (<10 pmol/l) and those with persistent C-peptide (either 10–200 pmol/l or 10–50 pmol/l). In addition, the relationship between self-reported hypoglycaemia and C-peptide was assessed (
n
= 167). Data are median (interquartile range).
Results
Individuals with preserved C-peptide secretion (10–200 pmol/l) had shorter duration of diabetes (15 9–24 vs 25 15–34 years,
p
< 0.001) and older age at diagnosis (23 14–28 vs 15 9–25 years,
p
< 0.001), although current age did not differ in this cohort. Preserved C-peptide was associated with lower time with glucose <3.9 mmol/l (3% 2–6% vs 5% 3–9%,
p
< 0.001), fewer low-glucose events per 2 week period (7 4–10 vs 10 5–16,
p
< 0.001), lower SD of glucose (3.8 3.4–4.2 vs 4.1 3.5–4.7 mmol/l,
p
= 0.017) and lower CV of glucose (38.0 35.0–41.6 vs 41.8 36.5–45.8,
p
< 0.001). These differences were also present in those with C-peptide 10–50 pmol/l and associations were independent of diabetes duration and estimated HbA
1c
in logistic regression analysis. Preserved C-peptide was also associated with lower rates of self-reported asymptomatic hypoglycaemia (8.0% vs 22.8% in the past month,
p
= 0.028).
Conclusions/interpretation
Preserved C-peptide secretion is associated with fewer low-glucose events and lower glucose variability on flash monitoring. This suggests that individuals with preserved C-peptide may more safely achieve intensive glycaemic targets.
Type 2 diabetes is associated with dementia, and also with more slight cognitive decrements. In this Review we discuss trajectories from normal cognition to dementia in people with type 2 diabetes, ...and explore opportunities for treatment. Slight diabetes-associated cognitive decrements and dementia affect different age groups and show a different evolution. These cognitive entities should therefore not be regarded as a continuum, although their effects might be additive. Vascular damage is a key underlying process in both entities. Glucose-mediated processes and other metabolic disturbances might also have a role. No treatment has been established, but management of vascular risk factors and optimisation of glycaemic control could have therapeutic benefit. We identify possible opportunities for intervention to improve cognitive outcomes in people with type 2 diabetes, and suggest how treatment can be tailored to individual risk profiles and comorbidities.
Cerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral ...microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes.
In the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60-75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale.
After age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease.
DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation.
Aim
To estimate the incidence of diabetic ketoacidosis (DKA) among pregnant women, describe its clinical features, management and outcomes and identify the risk factors for the condition.
Methods
A ...national population‐based case–control study was conducted in the UK using the UK Obstetric Surveillance System between April 2019 and September 2020 including all pregnant women with DKA irrespective of the level of blood glucose. The incidence rate of DKA in pregnancy was estimated. A case–control analysis limited to women with type 1 diabetes was performed comparing characteristics of women with DKA (cases) to those of women whose pregnancies were not complicated by DKA (controls).
Results
In all, 82 women were identified with DKA in pregnancy; 6.3 per 100,000 maternities (95% CI: 5.0–7.9). No maternal deaths occurred, but perinatal mortality was 12/73 (16%) with 11 stillbirths and one neonatal death. DKA episodes mostly occurred in women with type 1 diabetes (85%) and in the 3rd trimester of pregnancy (71%). Episodes were mainly precipitated by infection (21%), vomiting (21%), steroid therapy (13%) and medication errors (10%). Fifteen percent of women had more than one episode of DKA during their pregnancy. Risk factors associated with DKA among women with type 1 diabetes identified through the case–control analysis were the woman and/or partner not being in a paid employment and having at least one microvascular complication of diabetes before pregnancy.
Conclusion
DKA in pregnancy was associated with high perinatal mortality and was linked with factors related to socio‐economic deprivation, mental health problems and long‐term difficulties with glycaemic control.
OBJECTIVE: Type 2 diabetes is an established risk factor for development of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). We aimed to determine the prevalence and clinical ...correlates of these conditions in a large cohort of people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 939 participants, aged 61-76 years, from the Edinburgh Type 2 Diabetes Study (ET2DS)--a large, randomly selected population of people with type 2 diabetes--underwent liver ultrasonography. Ultrasound gradings of steatosis were compared with magnetic resonance spectroscopy in a subgroup. NAFLD was defined as hepatic steatosis in the absence of a secondary cause (screened by questionnaire assessing alcohol and hepatotoxic medication use, plasma hepatitis serology, autoantibodies and ferritin, and record linkage to determine prior diagnoses of liver disease). Binary logistic regression was used to analyze independent associations of characteristics with NAFLD. RESULTS: Hepatic steatosis was present in 56.9% of participants. After excluding those with a secondary cause for steatosis, the prevalence of NAFLD in the study population was 42.6%. Independent predictors of NAFLD were BMI, lesser duration of diabetes, HbA₁c, triglycerides, and metformin use. These remained unchanged after exclusion of participants with evidence of hepatic fibrosis from the group with no hepatic steatosis. CONCLUSIONS: Prevalences of hepatic steatosis and NAFLD were high in this unselected population of older people with type 2 diabetes, but lower than in studies in which ultrasound gradings were not compared with a gold standard. Associations with features of the metabolic syndrome could be used to target screening for this condition.
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