A high intake of fish oil moderately increases blood glucose and decreases insulin sensitivity in persons with type 2 diabetes without hypertriacylglycerolemia and alters carbohydrate and fat utilization in a time-dependent manner.

OBJECTIVEWe assessed adulthood cognition in relation to early exposure to severe hypoglycemia (SH).RESEARCH DESIGN AND METHODSSixteen years subsequent to a study of cognitive function in 28 diabetic children and 28 matched control subjects, we reexamined the same subjects with a 96% participation rate. Diabetic subjects were classified as with (n = 9) or without (n = 18) early (≤10 years of age) SH, which was defined as convulsions or loss of consciousness.RESULTSOverall, cognitive scores were 0.9 SDs lower in subjects with early SH compared with subjects without early SH (P = 0.003). The two diabetic groups particularly differed with respect to problem solving, verbal function, and psychomotor efficiency. Earlier age at first incident of SH was associated with poorer cognition (P for trend = 0.001).CONCLUSIONSThe findings suggest that early exposure to SH may have lasting and clinically relevant effects on cognition.

Variants in hepatocyte nuclear factor (HNF)-4␣ cause maturity-onset diabetes of the young, type 1 (MODY1) and may also be risk factors for type 2 diabetes. We sequenced the HNF4A gene of 95 MODY3-negative probands from the Norwegian MODY Registry. We found three novel coding variants in exon 8 of HNF4A: G326R, T339I, and W340X. In intron 7, we noted a single nucleotide polymorphism in the binding site of a previously published primer pair, which in some cases caused allelic drop out when amplifying exon 8. We also detected two novel sequence variants of the P2 promoter region, of which P2 ؊192C>G showed linkage with diabetes in two families (maximal logarithm of odds score of 3.1 and 0.8, respectively). This variant and a surrounding haplotype restricted by 3.7 Mb was also found in two Danish MODY pedigrees. The age of onset was higher in the P2 ؊192C>G carriers (median 45 years) compared with that reported for other MODY1 individuals. We could not support a biological role of the P2 promoter variant by in vitro transfection assays. In conclusion, we have identified three novel HNF4A mutations and a 3.7-Mb haplotype, including the HNF4A P2 promoter, which was linked with diabetes. Diabetes 55: 1899 -1903, 2006 M aturity-onset diabetes of the young (MODY) can result from disease-causing sequence variants in any of at least six different genes that encode the glycolytic enzyme glucokinase (GCK) and five transcription factors: hepatocyte nuclear factor (HNF)-1␣, -1␤, and -4␣, insulin promoter factor-1, and NEUROD1 (1). Recently, genetic variants in the ␤-cell-specific P2 promoter region of the HNF4A (MODY1) gene have gained substantial attention in MODY (2-5) and in type 2 diabetes (6 -12).We have investigated the prevalence of sequence variants of the HNF4A gene in probands recruited from the Norwegian MODY Registry (13) after first excluding the presence of mutations in HNF1A (MODY3). In clinically relevant cases, we had also excluded mutations in GCK (MODY2). Here, we present a summary of sequence variants detected during the screening and discuss their role in the development of monogenic diabetes. RESEARCH DESIGN AND METHODSSince 1997, physicians have referred subjects to the Norwegian MODY Registry based on at least two of the following criteria: 1) first-degree relative with diabetes, 2) onset of diabetes before age 25 years in at least one family member, 3) low dose of insulin requirement (Ͻ0.5 units ⅐ kg Ϫ1 ⅐ day Ϫ1 ), 4) early-onset diabetes defined as diabetes diagnosed between age 25 and 40 years, and 5) subjects with an unusual type 1 diabetes (low-dose insulin requirement, no antibodies, or atypical history). Obviously, the conventional criteria of MODY (1) are not met in all cases. Nevertheless, inclusion of subjects based only on the conventional criteria will exclude some true MODY patients, e.g., those with de novo mutations, age at diagnosis after age 25 years, or limited clinical data on the family history of diabetes.We sequenced HNF4A in 95 probands recruited from the Norwegian MODY Registr...

Aims/hypothesisThe aim of this study was to compare cognitive function in adults with type 1 diabetes who have impaired awareness of hypoglycaemia with those who have normal awareness of hypoglycaemia. A putative association was sought between cognitive test scores and a history of severe hypoglycaemia.MethodsA total of 68 adults with type 1 diabetes were included: 33 had impaired and 35 had normal awareness of hypoglycaemia, as confirmed by formal testing. The groups were matched for age, sex and diabetes duration. Cognitive tests of verbal memory, object-location memory, pattern separation, executive function, working memory and processing speed were administered.ResultsParticipants with impaired awareness of hypoglycaemia scored significantly lower on the verbal and object-location memory tests and on the pattern separation test (Cohen’s d −0.86 to −0.55 [95% CI −1.39, −0.05]). Participants with impaired awareness of hypoglycaemia had reduced planning ability task scores, although the difference was not statistically significant (Cohen’s d 0.57 [95% CI 0, 1.14]). Frequency of exposure to severe hypoglycaemia correlated with the number of cognitive tests that had not been performed according to instructions.Conclusions/interpretationImpaired awareness of hypoglycaemia was associated with diminished learning, memory and pattern separation. These cognitive tasks all depend on the hippocampus, which is vulnerable to neuroglycopenia. The findings suggest that hypoglycaemia contributes to the observed correlation between impaired awareness of hypoglycaemia and impaired cognition.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-017-4233-3) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

In this sample of Norwegian adults with type 1 diabetes, women expressed more concerns about hypoglycemia than men. The highest HFS-II-Worry scores occurred in the same items in women and men, but the largest gender differences in mean scores appeared across a variety of other items, some of which were related to social esteem.

People with type 1 diabetes and impaired awareness of hypoglycaemia (IAH) are prone to severe hypoglycaemia. Previous attempts to develop non-invasive hypoglycaemia alarm systems have shown promising results, but it is not known if such alarms can detect severe hypoglycaemia in people with IAH. We aimed to explore whether a combination of non-invasive sensors could reliably evaluate hypoglycaemia (plasma glucose (PG) minimum 2.5 mmol/L) in people with IAH. Twenty participants with type 1 diabetes and IAH underwent randomly ordered, single blinded hyperinsulinemic euglycaemic and hyperinsulinemic hypoglycaemic clamps. Sweating, skin temperature, ECG, counterregulatory hormones and symptoms of hypoglycaemia were assessed. Overall, we were not able to detect clamp-induced hypoglycaemia with sufficient sensitivity and specificity for further clinical use. As a post-hoc analysis, we stratified participants according to their ability to identify hypoglycaemic symptoms during hypoglycaemic clamps. Five out of 20 participants could identify such symptoms. These participants had a significantly higher adrenaline response to hypoglycaemia (p < 0.001) and were reliably identified by sensors. Based on our observations, a non-invasive alarm system based on measurement of sweating responses and ECG changes during hypoglycaemia might provide an alert at a plasma glucose concentration around 2.5 mmol/L if an adequate sympatho-adrenal reaction is elicited.

OBJECTIVEImpaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in people with insulin-treated diabetes; autonomic neuropathy has been suggested to underlie its development. The aim was to evaluate a putative association between IAH and autonomic dysfunction using novel and sensitive measures of autonomic neural function. RESEARCH DESIGN AND METHODSSixty-six adults with type 1 diabetes were studied, 33 with IAH and 33 with normal awareness of hypoglycemia (NAH), confirmed by formal testing. Participants were matched for age, sex, and diabetes duration. Clinical and laboratory evaluations included extensive autonomic function testing, peripheral nerve conduction studies, and quantitative sensory testing. Composite abnormality Z scores were used for group comparisons. RESULTSThe IAH and NAH group had similar median (interquartile range) age of 48 (14.5) vs. 47 (14.5) years, diabetes duration of 30 (13.5) vs. 31 (13.5) years, and mean 6 SD HbA 1c 7.8 6 2.2% vs. 8.1 6 1.9%, respectively. The autonomic composite Z score did not differ between the two groups (mean difference 20.15, 95% CI 20.46, 0.16; P = 0.33), nor did the thermal detection (mean difference 0.15, 95% CI 20.31, 0.61; P = 0.51) or nerve conduction scores (mean difference 0.03, 95% CI 20.43, 0.49; P = 0.89). CONCLUSIONSIn adults with type 1 diabetes, IAH was not associated with autonomic dysfunction or peripheral neuropathy.Impaired awareness of hypoglycemia (IAH), defined as a diminished ability to perceive the onset of hypoglycemia, is associated with an increased risk of severe hypoglycemia in people with insulin-treated diabetes (1-3). Elucidation of the pathogenesis of IAH may help to minimize the risk of severe hypoglycemia.The glycemic thresholds for counterregulatory responses, generation of symptoms, and cognitive impairment are reset at lower levels of blood glucose in people who have developed IAH (4). This cerebral adaptation appears to be induced by

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