Health professionals' views and experiences around the dietary and lifestyle management of gestational diabetes in New Zealand.

AIM: This study aimed to investigate New Zealand health professionals' views and experiences around the dietary and lifestyle management of gestational diabetes. METHODS: Semi-structured interviews were conducted remotely with health professionals; sessions were recorded and transcribed. Core themes were extracted using inductive thematic analysis using a framework method. RESULTS: Twenty-seven health professionals were interviewed (13 diabetes dietitians, 8 specialist diabetes midwives, 2 community midwives, 1 antenatal clinic midwife, 1 obstetrician and 2 endocrinologists). Themes were organised into three central domains: (a) Social and cultural barriers, (b) Service provision and (c) Nutrition advice. Enabling themes included professional collaboration, innovation and creating trusting and supportive environments. Key barriers identified included accessibility, cultural barriers, overwhelmed service, fragmentation and conflicting information and nutrition resource gaps. CONCLUSIONS: Findings highlight foremost a deficit in primary antenatal nutrition advice that may play a significant role in the fragmentation identified. Investment in community-inclusive services providing antenatal nutrition and diabetes education appears critical to overcome barriers associated with misinformation and poor outcomes. Pathways to include nutrition education from various primary care health providers should be investigated to ease the burden from specialist gestational diabetes clinicians and allow effective delegation of dietetic resources. Revision of current nutrition guidelines for the management of gestational diabetes in New Zealand is needed to facilitate consistent messaging and standards of care.

The role of maternal diet on offspring hyperinsulinaemia and adiposity after birth: a systematic review of randomised controlled trials.

In utero diet may be directly related to the risk of fetal hyperinsulinaemia and offspring metabolic health. This review examines the relationship between maternal dietary exposures and sub-clinical fetal hyperinsulinaemia and neonatal adiposity. Articles were identified in MEDLINE, Web of Science, Cochrane Controlled Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, SCOPUS, and SPORTDiscus (September 2019-March 2021) using the preferred reporting items for systematic reviews and meta-analyses guidelines. PROSPERO registration ID CRD42020146453. Studies were selected by two independent reviewers. Randomised controlled trials (RCT) involving a dietary intervention with pregnant women (healthy pregnancy, gestational diabetes mellitus and obesity) and reporting fetal cord-blood insulin, c-peptide, glucose or adiposity estimates were included. One author extracted all information on main study characteristics and outcomes. Risk of bias was assessed using the Cochrane Collaboration's bias risk assessment tool. A total of 733 articles were identified. Fourteen articles from 11 RCTs (3614 participants) were included. Studies reviewed showed no specific effect of maternal diet on neonatal cord blood insulin, c-peptide or glucose levels. Infants born to mothers who followed a low glycaemic load (GL) had lower skin fold thickness compared to controls. Interventions that provided individualised nutrition counselling to women with obesity or previous infant born > 4 kg were also associated with lower adiposity. The studies reviewed suggest that lifestyle-based dietary interventions to improve glycaemia (low GL) have a protective effect against excess adiposity. Future studies should incorporate multi-modal interventions with dietary counselling to support lifestyle changes throughout gestation and include assessments of maternal insulin resistance at recruitment.

Rethinking Fragility Fractures in Type 2 Diabetes: The Link between Hyperinsulinaemia and Osteofragilitas.

Patients with type 2 diabetes mellitus (T2DM) and/or cardiovascular disease (CVD), conditions of hyperinsulinaemia, have lower levels of osteocalcin and bone remodelling, and increased rates of fragility fractures. Unlike osteoporosis with lower bone mineral density (BMD), T2DM bone fragility "hyperinsulinaemia-osteofragilitas" phenotype presents with normal to increased BMD. Hyperinsulinaemia and insulin resistance positively associate with increased BMD and fragility fractures. Hyperinsulinaemia enforces glucose fuelling, which decreases NAD+-dependent antioxidant activity. This increases reactive oxygen species and mitochondrial fission, and decreases oxidative phosphorylation high-energy production capacity, required for osteoblasto/cytogenesis. Osteocytes directly mineralise and resorb bone, and inhibit mineralisation of their lacunocanalicular space via pyrophosphate. Hyperinsulinaemia decreases vitamin D availability via adipocyte sequestration, reducing dendrite connectivity, and compromising osteocyte viability. Decreased bone remodelling and micropetrosis ensues. Trapped/entombed magnesium within micropetrosis fossilisation spaces propagates magnesium deficiency (MgD), potentiating hyperinsulinaemia and decreases vitamin D transport. Vitamin D deficiency reduces osteocalcin synthesis and favours osteocyte apoptosis. Carbohydrate restriction/fasting/ketosis increases beta-oxidation, ketolysis, NAD+-dependent antioxidant activity, osteocyte viability and osteocalcin, and decreases excess insulin exposure. Osteocalcin is required for hydroxyapatite alignment, conferring bone structural integrity, decreasing fracture risk and improving metabolic/endocrine homeodynamics. Patients presenting with fracture and normal BMD should be investigated for T2DM and hyperinsulinaemia.

Metabolic Phenotypes and Step by Step Evolution of Type 2 Diabetes: A New Paradigm.

Unlike bolus insulin secretion mechanisms, basal insulin secretion is poorly understood. It is essential to elucidate these mechanisms in non-hyperinsulinaemia healthy persons. This establishes a baseline for investigation into pathologies where these processes are dysregulated, such as in type 2 diabetes (T2DM), cardiovascular disease (CVD), certain cancers and dementias. Chronic hyperinsulinaemia enforces glucose fueling, depleting the NAD+ dependent antioxidant activity that increases mitochondrial reactive oxygen species (mtROS). Consequently, beta-cell mitochondria increase uncoupling protein expression, which decreases the mitochondrial ATP surge generation capacity, impairing bolus mediated insulin exocytosis. Excessive ROS increases the Drp1:Mfn2 ratio, increasing mitochondrial fission, which increases mtROS; endoplasmic reticulum-stress and impaired calcium homeostasis ensues. Healthy individuals in habitual ketosis have significantly lower glucagon and insulin levels than T2DM individuals. As beta-hydroxybutyrate rises, hepatic gluconeogenesis and glycogenolysis supply extra-hepatic glucose needs, and osteocalcin synthesis/release increases. We propose insulin's primary role is regulating beta-hydroxybutyrate synthesis, while the role of bone regulates glucose uptake sensitivity via osteocalcin. Osteocalcin regulates the alpha-cell glucagon secretory profile via glucagon-like peptide-1 and serotonin, and beta-hydroxybutyrate synthesis via regulating basal insulin levels. Establishing metabolic phenotypes aids in resolving basal insulin secretion regulation, enabling elucidation of the pathological changes that occur and progress into chronic diseases associated with ageing.

Hyperinsulinemia during pregnancy across varying degrees of glucose tolerance: An examination of the Kraft database.

AIM: Hyperinsulinemia is a known underlying driver of metabolic disease; however, its role in pregnancy complications is less understood due to insulin measurement not being a part of standard clinical assessments. This study aimed to characterize hyperinsulinemia in pregnancy by gestational diabetes (GD) status using Kraft methodology. METHODS: We analyzed historical data from 926 pregnant women who underwent a 100-g oral glucose tolerance test (OGTT), which included insulin measurement. Subjects were grouped by GD diagnosis status ("Normal", "Borderline", "GD") and insulin responses over 3 h were compared between groups. RESULTS: "GD" was diagnosed in 20.3% of the subjects and 13.8% were grouped as "Borderline." The prevalence of hyperinsulinemia using the Kraft algorithm was 33.1% for Kraft IIB and 42.0% for Kraft III. Compared to normal glucose-tolerant mothers, individuals from the "Borderline" group had an exacerbated insulin response, although not to the same magnitude as those with "GD." CONCLUSIONS: Dynamic OGTT insulin measurement during pregnancy may provide a meaningful assessment of metabolic risk among women who would otherwise not be diagnosed with GD.

Relationships between hyperinsulinaemia, magnesium, vitamin D, thrombosis and COVID-19: rationale for clinical management.

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.

Can the Molar Insulin: C-Peptide Ratio Be Used to Predict Hyperinsulinaemia?

Hyperinsulinaemia is the precursor to numerous metabolic disorders. Early diagnosis and intervention could improve population health. Diagnosing hyperinsulinaemia is problematic because insulin has a very short half-life (2-5minutes). It is theorised that c-peptide levels (half-life 20-30minutes) would be a better proxy for insulin due to both hormones being released in equimolar amounts. However, the correlation between c-peptide and insulin levels is unknown. We aim to identify their correlation following a four-hour oral glucose tolerance test (OGTT). Data were obtained from records of routine medical care at St Joseph's Hospital, Chicago, IL, USA, during 1977. Two hundred and fifty-five male and female participants aged over 20 years undertook a fourhour OGTT with plasma glucose, insulin and c-peptide levels recorded. Correlation was assessed with Pearson's correlation. There was a weak correlation between insulin and c-peptide, which increased to moderate across the four-hour OGTT (r = 0.482-0.680). There was no significant change in this relationship when data was subdivided according to either the WHO glucose status or Kraft insulin response. Although there was a correlation between insulin and c-peptide, it was too weak to recommend the use of c-peptide as an alternative biomarker for the diagnosis of hyperinsulinaemia.

Low-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: A randomised clinical trial.

BACKGROUND: Low-carbohydrate, high-fat (LCHF) diets are useful for treating a range of health conditions, but there is little research evaluating the degree of carbohydrate restriction on outcome measures. This study compares anthropometric and cardiometabolic outcomes between differing carbohydrate-restricted diets. OBJECTIVE: Our hypothesis was that moderate carbohydrate restriction is easier to maintain and more effective for improving cardiometabolic health markers than greater restriction. DESIGN: A total of 77 healthy participants were randomised to a very low-carbohydrate ketogenic diet (VLCKD), low-carbohydrate diet (LCD), or moderate-low carbohydrate diet (MCD), containing 5%, 15% and 25% total energy from carbohydrate, respectively, for 12-weeks. Anthropometric and metabolic health measures were taken at baseline and at 12 weeks. Using ANOVA, both within and between-group outcomes were analysed. RESULTS: Of 77 participants, 39 (51%) completed the study. In these completers overall, significant reductions in weight and body mass index occurred ((mean change) 3.7 kg/m2; 95% confidence limits (CL): 3.8, 1.8), along with increases in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, (0.49 mmol/L; 95% CL; 0.06, 0.92; p = 0.03), and total cholesterol concentrations (0.11 mmol/L; 95% CL; 0.00, 0.23; p = 0.05). Triglyceride (TG) levels were reduced by 0.12 mmol/L (95% CL; -0.20, 0.02; p = 0.02). No significant changes occurred between groups. The largest improvements in high density lipoprotein cholesterol (HDL-c) and TG and anthropometric changes occurred for the VLCKD group. CONCLUSIONS: Low-carbohydrate, high-fat diets have a positive effect on markers of health. Adherence to the allocation of carbohydrate was more easily achieved in MCD, and LCD groups compared to VLCKD and there were comparable improvements in weight loss and waist circumference and greater improvements in HDL-c and TG with greater carbohydrate restriction.

Identifying hyperinsulinaemia in the absence of impaired glucose tolerance: An examination of the Kraft database.

OBJECTIVE: Hyperinsulinaemia is associated with development of chronic metabolic disease and is emerging as a health risk independent to that of insulin resistance. However, little is known to what extent hyperinsulinaemia occurs with normal glucose tolerance in lean subjects. METHOD: Oral glucose tolerance tests with concurrent insulin assay were conducted during the 1970s-1990s. Participants were classified according to glucose tolerance and insulin response pattern. Analysis of variance compared differences in plasma glucose, plasma insulin, and demographic and metabolic risk factors between groups. RESULTS: Participants with normal glucose tolerance comprised 54% (n=4185) of the total cohort. Of these, just over half (n=2079) showed hyperinsulinaemia despite normal glucose clearance. Obesity had a modest association with hyperinsulinaemia in people with normal glucose tolerance. Fasting insulin had limited value in diagnosing hyperinsulinaemia. The majority of participants (93%) with impaired glucose tolerance or diabetes had concurrent hyperinsulinaemia. CONCLUSION: Hyperinsulinaemia in the absence of impaired glucose tolerance may provide the earliest detection for metabolic disease risk and likely occurs in a substantial proportion of an otherwise healthy population. Dynamic insulin patterning may produce more meaningful and potentially helpful diagnoses. Further research is needed to investigate clinically useful hyperinsulinaemia screening tools.