Perceptions and experiences of living with coexisting type 2 diabetes and severe mental illness: a scoping review.

AIMS: To map existing research-based knowledge of everyday life and illness management among people with coexisting type 2 diabetes and severe mental illness, and to identify study designs, aims, populations and themes. METHODS: A systematic literature search was performed on 16 April 2019 using Medline, Embase, PsycINFO, Cinahl, the Cochrane Library, and the Web of Science to conduct a scoping review. Included studies were summarized with regard to the quantity of research, the study designs, aims, populations and themes RESULTS: From 3406 records, we included 23 studies about everyday life and illness management among people with coexisting type 2 diabetes and severe mental illness. Four studies were qualitative (observations, interviews and focus groups), and 19 were quantitative (observational and interventions) and used questionnaires. Five themes emerged in the findings: (1) diet and exercise, but not other diabetes self-care activities, are consistently compromised in the target group; (2) psychiatric exacerbation diminishes diabetes self-care; (3) social support and high self-efficacy improve diabetes self-care; (4) use of healthcare services is compromised; and (5) quality of life and well-being is poor. CONCLUSIONS: The limited research into the studied population's experiences with coexisting type 2 diabetes and severe mental illness is characterized by its heterogeneity in aims and methods and a strong focus on diabetes management and treatment. Further research focusing on the management of both conditions in everyday life is needed to improve specialized and integrated care targeting the population.

Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function.

Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) are known to cause a rare subtype of maturity-onset diabetes of the young (MODY5), which is associated with early-onset progressive non-diabetic renal dysfunction. To investigate whether mutations in HNF-1 are implicated in the pathogenesis of MODY or late-onset diabetes with and without nephropathy in Danish Caucasians we examined the HNF-1beta (TCF2) and the dimerization cofactor of HNF-1 (DCoH, PCBD) genes for mutations in 11 MODY probands, 28 type 2 diabetic patients with nephropathy, and 46 type 2 diabetic patients with an impaired beta-cell function by combined single-strand conformation polymorphism (SSCP) and heteroduplex analysis. Analysis of the promoter and nine exons including intron-exon boundaries of the HNF-1beta gene revealed one novel silent polymorphism and three previously reported intronic variants. The silent polymorphism (I91I) was found in one patient with late-onset type 2 diabetes. One of the intronic variant (IVS6+26T-->C) was examined further. Among 584 type 2 diabetic patients the allelic frequency was 13.1% (11.2-15.0%) compared to 11.6% (8.6-14.5%) in 229 glucose tolerant control subjects (NS). No difference in insulin secretion during an OGTT was seen between carriers of the different IVS6+26T-->C genotypes among the 229 middle-aged control subjects, nor among 302 glucose tolerant 60-year-old Danish Caucasians. Mutation analysis of the four exons comprising the DCoH gene revealed a previously described A-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects.

Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus.

AIM/HYPOTHESIS: This study aimed to investigate if variability in the peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) gene is associated with Type II (non-insulin-dependent) diabetes mellitus. METHODS: The PGC-1 gene was examined in 53 Type II diabetic patients applying single strand conformational polymorphism analysis followed by nucleotide sequencing. Identified variants were genotyped in an association study comprising 483 Type II diabetic patients and 216 glucose-tolerant control subjects. A replication study was done in an additional 201 Type II diabetic patients and 293 glucose-tolerant subjects. Furthermore, a potential interaction between the Pro12Ala polymorphism of PPAR-gamma2 and the PGC-1 Gly482Ser variant on risk of Type II diabetes was investigated. RESULTS: A total of seven variants (Ser74Leu, IVS2 + 52C-->A, Thr394Thr, Asp475Asp, Gly482Ser, Thr528Thr, and Thr612Met) were identified and investigated in an association study. Six of the variants showed no association with Type II diabetes in the initial study. However, the Gly482Ser polymorphism, was more frequent among Type II diabetic patients (37.0 %) than among glucose-tolerant subjects (30.8 %) (p = 0.032). In a replication study the difference in allele frequencies of the Gly482Ser variant remained significant (p = 0.0135). The combined study yielded an allele frequency of 37.3 % (34.7-39.9) for Type II diabetic patients and 30.5 % (27.7-33.4) for glucose-tolerant subjects (p = 0.0007). No interaction between this variant and the Pro12Ala polymorphism of PPAR-gamma2 was observed. CONCLUSION/INTERPRETATION: A widespread Gly482Ser polymorphism of PGC-1 is associated with a 1.34 genotype relative risk of Type II diabetes.

Lack of impact of low-dose acetylsalicylic acid on kidney function in type 1 diabetic patients with microalbuminuria.

OBJECTIVE: High-dose treatment with cyclooxygenase inhibitors reduces urinary albumin excretion rate (AER) in type 1 diabetic patients with microalbuminuria and macroalbuminuria. This effect may lead to an incorrect classification of albuminuria (normo-, micro-, and macroalbuminuria) and jeopardize the monitoring of antiproteinuric treatment (e.g., ACE inhibition). Whether similar difficulties exist using low-dose acetylsalicylic acid (ASA), now widely recommended for primary and secondary prevention of cardiovascular events in type 1 diabetic patients with micro- and macroalbuminuria, remains to be elucidated. RESEARCH DESIGN AND METHODS: We performed a randomized double-blind crossover trial in 17 type 1 diabetic patients with microalbuminuria (urinary AER 30-300 mg/24 h). Patients were given ASA (150 mg/daily) for 4 weeks followed by placebo for 4 weeks with at least a 2-week washout period in random order. At the end of each treatment period, AER (enzyme-linked immunosorbent assay), glomerular filtration rate (GFR) (plasma clearance of 51Cr-EDTA), blood pressure (BP) (Hawksley), and HbA1c (by high-performance liquid chromatography) were measured. Patients were advised to follow a normal diabetes diet without sodium restriction and received their usual antihypertensive treatment during the investigation. RESULTS: During the study (ASA vs. placebo), urinary AER (geometric mean 64 [95% CI 39-105] vs. 59 [40-87] mg/24 h), GFR (mean 106 [93-118] vs. 104 [90-117] ml x min(-1) x 1.73 m(-2)), systolic BP (mean 130 [119-141] vs. 130 [119-142] mmHg), diastolic BP (mean 71 [65-78] vs. 71 [64-78] mmHg), and HbA1c (mean 8.4% [8.0-9.0] vs. 8.5% [8.1-9.0]) remained unchanged. CONCLUSIONS: Treatment with 150 mg ASA daily does not have any impact on AER or GFR in type 1 diabetic patients with microalbuminuria. Consequently, primary and secondary prevention of cardiovascular events with low-dose ASA does not interfere with the classification of AER or monitoring of antiproteinuric treatment in such patients.

[Intensified treatment of type 2 diabetes mellitus. Is polypharmacy necessary and justified?]. / Intensiveret behandling at type 2-diabetes mellitus. Er polyfarmaci nødvendig og berettiget?

Newly published randomised controlled trials with pharmacological intervention against hyperglycaemia, hypertension and dyslipidemia have challenged the traditional empiric treatment of type 2-diabetes. This review focuses on the results of these trials as well as randomised trials with pharmacological therapy of microalbuminuria, primary prevention with acetylsalicylic acid and angiotensin converting enzyme (ACE) inhibitors. The overall results from these trials are clinically relevant reductions in the risk of late diabetic complications. Taken together, the new clinical knowledge does not mean that all patients with type 2-diabetes besides relevant changes in lifestyle will benefit from a comprehensive polypharmacy. It means, however, that based upon the individual risk profile the medical professionals have to motivate the patient for an evidence based "therapeutic package" which is likely to improve the longterm outcome.

[Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno-2 study]. / Intensiveret multifaktoriel intervention hos patienter med type 2-diabetes mellitus og mikroalbuminuri: Steno-2-studiet.

We carried out a randomized trial of stepwise intensive treatment or standard treatment of risk factors in patients with type 2 diabetes and microalbuminuria. Patients were allocated standard treatment (n = 80) or intensive treatment (n = 80). Intensive treatment was a stepwise implementation of behaviour modification, pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia, and microalbuminuria. The primary endpoint was development of nephropathy. Secondary endpoints were incidence or progression of diabetic retinopathy and neuropathy. Patients were followed for 3.8 years. The intensive group had significantly lower rates of progression to hephropathy (odds ratio 0.27 [95% CI 0.10-0.75]), progression of retinopathy (0.45 (0.21-0.95]), and progression of autonomic neuropathy (0.32 [0.12-0.78]). In conclusion, intensified multifactorial intervention in patients with type 2 diabetic mellitus and microalbuminuria has beneficial effects on long-term complications.

[Diaphragm-like strictures of the small intestine after treatment with non-steroidal anti-inflammatory agents]. / Diaphragmalignende tyndtarmsstrikturer efter behandling med ikkesteroide antiinflammatoriske stoffer.

Although final proof of a causal relationship is missing, it is believed that NSAID-induced lesions in the distal gut are common. We present a case where nine years of NSAID treatment appears to have caused characteristic, membrane-like strictures of the small intestine, and give a brief discussion of the possible pathogenetic mechanisms.