Phyiscal Activity and Pregnancy

First article looked at today concludes:

This meta-analysis suggests that higher leisure-time activity is associated with reduced risk of preterm birth. 

So, there is a possibility that a certain degree of physical activity reduces the chances that the mother will have  a preterm birth.  

What about gestational diabetes?  See here, abstract:

Physical activity has been inconsistently associated with risk of gestational diabetes mellitus in epidemiological studies, and questions remain about the strength and shape of the dose-response relationship between the two. We therefore conducted a systematic review and meta-analysis of cohort studies and randomized trials on physical activity and gestational diabetes mellitus. PubMed, Embase and Ovid databases were searched for cohort studies, and randomized controlled trials of physical activity and risk of gestational diabetes mellitus, up to August 5th 2015. Summary relative risks (RRs) were estimated using a random effects model. Twenty-five studies (26 publications) were included. For total physical activity the summary RR for high versus low activity was 0.62 (95 % CI 0.41-0.94, I2 = 0 %, n = 4) before pregnancy, and 0.66 (95 % CI 0.36-1.21, I2 = 0 %, n = 3) during pregnancy. For leisure-time physical activity the respective summary RRs for high versus low activity was 0.78 (95 % CI 0.61-1.00, I2 = 47 %, n = 8) before pregnancy, and it was 0.80 (95 % CI 0.64-1.00, I2 = 17 %, n = 17) during pregnancy. The summary RR for pre-pregnancy activity was 0.70 (95 % CI 0.49-1.01, I2 = 72.6 %, n = 3) per increment of 5 h/week and for activity during pregnancy was 0.98 (95 % CI 0.87-1.09, I2 = 0 %, n = 3) per 5 h/week. There was evidence of a nonlinear association between physical activity before pregnancy and the risk of gestational diabetes mellitus, pnonlinearity = 0.005, with a slightly steeper association at lower levels of activity although further reductions in risk were observed up to 10 h/week. There was also evidence of nonlinearity for physical activity in early pregnancy, pnonlinearity = 0.008, with no further reduction in risk above 8 h/week. There was some indication of inverse associations between walking (before and during pregnancy) and vigorous activity (before pregnancy) and the risk of gestational diabetes mellitus. This meta-analysis suggests that there is a significant inverse association between physical activity before pregnancy and in early pregnancy and the risk of gestational diabetes mellitus. Further studies are needed to clarify the association between specific types and intensities of activity and gestational diabetes mellitus.

So it seems physical activity can be helpful there as well. Of course, for both articles, this is for the general population; there may be individual cases where physical activity is restricted during pregnancy for health reasons.  

MicroRNA Biomarkers for Type I Diabetes

Here is a paper from several years ago suggesting that circulating microRNAs (small RNA molecules that affect gene expression) can be used to "predict and diagnose" type I diabetes before clinical symptoms are present.  Abstract:

Type 1 diabetes (T1D) is an autoimmune disease that is clinically silent until the majority of β cells are destroyed. There is an unmet need for reliable and cost-effective biomarkers to predict and diagnose diabetes at an early stage. A number of stable microRNAs (miRNAs) have been reported in serum and plasma and are now being investigated as biomarkers of different diseases. We measured the levels of 745 miRNAs in sera of children with recent-onset T1D and age-matched controls using locked nucleic acid-enhanced (LNA-enhanced) quantitative PCR profiling. Thirty-five miRNAs were significantly different between the groups, and 27 miRNAs were elevated in T1D. Good discriminating power was obtained for 6 miRNAs (miR-454-3p, miR-222-3p, miR-144-5p, miR-345-5p, miR-24-3p, and miR-140-5p), which were not elevated at later stages of diabetes. In silico pathway analysis, based on inferred miRNA target genes, associated glycosaminoglycan biosynthesis as well as PI3K/Akt, MAPK, and Wnt signaling pathways with early stages of T1D. Among the 27 upregulated miRNAs in T1D, 2 miRNAs significantly correlated with hemoglobin A1c (HbA1c), as did 5 of 8 downregulated miRNAs. A total of 134 miRNAs significantly correlated with HbA1c when stratifying hyperglycemia-induced miRNAs from T1D-specific miRNAs. In conclusion, we have identified a serum miRNA pattern of recent-onset T1D and signaling pathways that may be involved in its pathogenesis.

The same principle can apply for early diagnosis of other disorders, and we'll be looking at any progress (if any) made since this article came out.  Note also that study of microRNAs is not only useful for identifying biomarkers but also for identifying the cell signaling that is aberrant in disease (as the end of the abstract suggests), leading the way to possible novel therapies.

Artificial Sweeteners And Type 2 Diabetes Study

Here is an article on artificial sweeteners and type 2 diabetes risk.  Abstract:

BACKGROUND:

The influence of artificial sweeteners on metabolic diseases is controversial. Artificially sweetened beverages have been associated with an increased risk of type 2 diabetes (T2D) but biases and reverse causation have been suspected to have influenced the observed association. In addition, it has been suggested that investigation into the relationship between the frequency and duration of the consumption of packet or tablet artificial sweeteners and T2D risk is necessary.

METHODS:

We used data from 61,440 women in the prospective E3N-European Prospective Investigation into Cancer and Nutrition study, conducted between 1993 and 2011. We estimated hazards ratios (HRs) and 95% CIs of T2D risk associated with both the frequency and the duration of use of artificial sweeteners consumed in packets or tablets.

RESULTS:

Compared to "never or rare" consumers of artificial sweeteners, those using them "always or almost always" had an increased risk of T2D (HR = 1.83 [95% CI 1.66-2.02] in the multivariate model [MM], HR = 1.33 [95% CI 1.20-1.47] when further adjusted for body mass index, BMI). Women consuming artificial sweeteners in packets or tablets for more than 10 years also had an increased risk of T2D compared to never or rare users (HR = 2.10 [95% CI 1.83-2.40] in the MM and HR = 1.15 [95% CI 1.00-1.33] when adjusted for BMI, respectively).

CONCLUSIONS:

Our data suggest that both a higher frequency and a longer consumption of artificial sweeteners in packets or tablets was associated with T2D risk, independently of major T2D risk factors, but partially mediated by adiposity. A precautionary principle should be applied to the promotion of these products that are still largely recommended as healthy sugar substitutes.

A reasonable strategy may be to not use such artificial sweeteners and cut down on sugar in your diet as well. Avoid diabetes, and your health will thank you for it.

Dioscin And Diabetes

Dioscin can help alleviate negative effects of high glucose in type 2 diabetes through preserving pancreatic cells, mediated by effects on Wnt signaling.  Abstract:

BACKGROUND:

Dysfunction of pancreatic beta cells is related with type 2 diabetes mellitus. Dioscin, a natural steroid saponin, has many pharmacological effects. The aim of this study was to investigate the effects of dioscin on apoptosis of pancreatic beta cells induced by high glucose.

METHODS:

Pancreatic cell line RNAKT-15 was treated with 20 mM glucose with or without different concentrations of dioscin and viability and apoptosis of cells were measured. Western blot assay was used to measure the expression levels of some proteins such as phosphorylated glycogen synthase kinase 3β (GSK-3β) and β-catenin. Enzymelinked immunosorbent assay (ELISA) was used to detect the pro-inflammatory cytokines.

RESULTS:

High-glucose could significantly increase cell RNAKT-15 apoptosis and reduce cell viability (p < 0.01). Dioscin could improve the cell degeneration (p < 0.05). The results demonstrated that high-glucose could increase the proinflammatory cytokines, such as tumor necrosis factor α (TNF-α), interferon-γ (INF-γ), and transforming growth factor-β (TGF-β), while these effects were reduced when treated with dioscin (p < 0.05). Western blot results demonstrated that high-glucose affects p-GSK 3β and β-catenin expression levels (p < 0.01) and dioscin could significantly reduce these two protein levels (p < 0.05).

CONCLUSIONS:

The effects of dioscin against high-glucose induced apoptosis of pancreatic cells may occur through the Wnt signaling pathway. High-glucose led to increased pancreatic cell apoptosis and dioscin could attenuate these impairments. These findings highlight an important role of dioscin in the treatment potential of type 2 diabetes mellitus (T2DM).

Fad Diets Not Necessary

More support for the ides that “fad” diets – like low carb – are not necessary for weight control and dealing with metabolic syndrome. Take home point: “any diet type resulting in reduced energy intake will result in weight loss and related favorable metabolic and functional changes.”  Abstract:

In the past, different types of diet with a generally low-carbohydrate content (< 50-< 20 g/day) have been promoted, for weight loss and diabetes, and the effectiveness of a very low dietary carbohydrate content has always been a matter of debate. A significant reduction in the amount of carbohydrates in the diet is usually accompanied by an increase in the amount of fat and to a lesser extent, also protein. Accordingly, using the term "low carb-high fat" (LCHF) diet is most appropriate. Low/very low intakes of carbohydrate food sources may impact on overall diet quality and long-term effects of such drastic diet changes remain at present unknown. This narrative review highlights recent metabolic and clinical outcomes of studies as well as practical feasibility of low LCHF diets. A few relevant observations are as follows: (1) any diet type resulting in reduced energy intake will result in weight loss and related favorable metabolic and functional changes; (2) short-term LCHF studies show both favorable and less desirable effects; (3) sustained adherence to a ketogenic LCHF diet appears to be difficult. A non-ketogenic diet supplying 100-150 g carbohydrate/day, under good control, may be more practical. (4) There is lack of data supporting long-term efficacy, safety and health benefits of LCHF diets. Any recommendation should be judged in this light. (5) Lifestyle intervention in people at high risk of developing type 2 diabetes, while maintaining a relative carbohydrate-rich diet, results in long-term prevention of progression to type 2 diabetes and is generally seen as safe.

Insulin For Gestational Diabetes

This paper may be of interest for those who have gestational diabetes.  Abstract:

BACKGROUND:

Gestational diabetes mellitus (GDM) is associated with short- and long-term complications for the mother and her infant. Women who are unable to maintain their blood glucose concentration within pre-specified treatment targets with diet and lifestyle interventions will require anti-diabetic pharmacological therapies. This review explores the safety and effectiveness of insulin compared with oral anti-diabetic pharmacological therapies, non-pharmacological interventions and insulin regimens.

OBJECTIVES:

To evaluate the effects of insulin in treating women with gestational diabetes.

SEARCH METHODS:

We searched Pregnancy and Childbirth's Trials Register (1 May 2017), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (1 May 2017) and reference lists of retrieved studies.

SELECTION CRITERIA:

We included randomised controlled trials (including those published in abstract form) comparing:a) insulin with an oral anti-diabetic pharmacological therapy;b) with a non-pharmacological intervention;c) different insulin analogues;d) different insulin regimens for treating women with diagnosed with GDM.We excluded quasi-randomised and trials including women with pre-existing type 1 or type 2 diabetes. Cross-over trials were not eligible for inclusion.

DATA COLLECTION AND ANALYSIS:

Two review authors independently assessed study eligibility, risk of bias, and extracted data. Data were checked for accuracy.

MAIN RESULTS:

We included 53 relevant studies (103 publications), reporting data for 7381 women. Forty-six of these studies reported data for 6435 infants but our analyses were based on fewer number of studies/participants.Overall, the risk of bias was unclear; 40 of the 53 included trials were not blinded. Overall, the quality of the evidence ranged from moderate to very low quality. The primary reasons for downgrading evidence were imprecision, risk of bias and inconsistency. We report the results for our maternal and infant GRADE outcomes for the main comparison. Insulin versus oral anti-diabetic pharmacological therapyFor the mother, insulin was associated with an increased risk for hypertensive disorders of pregnancy (not defined) compared to oral anti-diabetic pharmacological therapy (risk ratio (RR) 1.89, 95% confidence interval (CI) 1.14 to 3.12; four studies, 1214 women; moderate-quality evidence). There was no clear evidence of a difference between those who had been treated with insulin and those who had been treated with an oral anti-diabetic pharmacological therapy for the risk of pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 studies, 2060 women; moderate-quality evidence); the risk of birth by caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 studies, 1988 women; moderate-quality evidence); or the risk of developing type 2 diabetes (metformin only) (RR 1.39, 95% CI 0.80 to 2.44; two studies, 754 women; moderate-quality evidence). The risk of undergoing induction of labour for those treated with insulin compared with oral anti-diabetic pharmacological therapy may possibly be increased, although the evidence was not clear (average RR 1.30, 95% CI 0.96 to 1.75; three studies, 348 women; I² = 32%; moderate-quality of evidence). There was no clear evidence of difference in postnatal weight retention between women treated with insulin and those treated with oral anti-diabetic pharmacological therapy (metformin) at six to eight weeks postpartum (MD -1.60 kg, 95% CI -6.34 to 3.14; one study, 167 women; low-quality evidence) or one year postpartum (MD -3.70, 95% CI -8.50 to 1.10; one study, 176 women; low-quality evidence). The outcomes of perineal trauma/tearing or postnatal depression were not reported in the included studies.For the infant, there was no evidence of a clear difference between those whose mothers had been treated with insulin and those treated with oral anti-diabetic pharmacological therapies for the risk of being born large-for-gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 studies, 2352 infants; moderate-quality evidence); the risk of perinatal (fetal and neonatal death) mortality (RR 0.85; 95% CI 0.29 to 2.49; 10 studies, 1463 infants; low-quality evidence);, for the risk of death or serious morbidity composite (RR 1.03, 95% CI 0.84 to 1.26; two studies, 760 infants; moderate-quality evidence); the risk of neonatal hypoglycaemia (average RR 1.14, 95% CI 0.85 to 1.52; 24 studies, 3892 infants; low-quality evidence); neonatal adiposity at birth (% fat mass) (mean difference (MD) 1.6%, 95% CI -3.77 to 0.57; one study, 82 infants; moderate-quality evidence); neonatal adiposity at birth (skinfold sum/mm) (MD 0.8 mm, 95% CI -2.33 to 0.73; random-effects; one study, 82 infants; very low-quality evidence); or childhood adiposity (total percentage fat mass) (MD 0.5%; 95% CI -0.49 to 1.49; one study, 318 children; low-quality evidence). Low-quality evidence also found no clear differences between groups for rates of neurosensory disabilities in later childhood: hearing impairment (RR 0.31, 95% CI 0.01 to 7.49; one study, 93 children), visual impairment (RR 0.31, 95% CI 0.03 to 2.90; one study, 93 children), or any mild developmental delay (RR 1.07, 95% CI 0.33 to 3.44; one study, 93 children). Later infant mortality, and childhood diabetes were not reported as outcomes in the included studies.We also looked at comparisons for regular human insulin versus other insulin analogues, insulin versus diet/standard care, insulin versus exercise and comparisons of insulin regimens, however there was insufficient evidence to determine any differences for many of the key health outcomes. Please refer to the main results for more information about these comparisons.

AUTHORS' CONCLUSIONS:

The main comparison in this review is insulin versus oral anti-diabetic pharmacological therapies. Insulin and oral anti-diabetic pharmacological therapies have similar effects on key health outcomes. The quality of the evidence ranged from very low to moderate, with downgrading decisions due to imprecision, risk of bias and inconsistency.For the other comparisons of this review (insulin compared with non-pharmacological interventions, different insulin analogies or different insulin regimens), there is insufficient volume of high-quality evidence to determine differences for key health outcomes.Long-term maternal and neonatal outcomes were poorly reported for all comparisons.The evidence suggests that there are minimal harms associated with the effects of treatment with either insulin or oral anti-diabetic pharmacological therapies. The choice to use one or the other may be down to physician or maternal preference, availability or severity of GDM. Further research is needed to explore optimal insulin regimens. Further research could aim to report data for standardised GDM outcomes.

Type 2 Diabetes, SNPs, And Wnt Signaling

Identification of genetic variants (SNPs) found in humans associated with type 2 diabetes (T2D) has shown some associated with Wnt signaling, which has been previously identified as linked to changes in T2D metabolism   Abstract:

Clinical studies in type 2 diabetes (T2D) primarily focused on the single nucleotide polymorphisms (SNPs) located in protein-coding regions. Recently, the SNPs located in noncoding regions have also been recognized to play an important role in disease susceptibility. The super enhancer is a cluster of transcriptional enhancers located in noncoding regions. It plays a critical role in cell-type specific gene expression. However, the exact mechanism of the super enhancer SNPs for T2D remains unclear. In this study, we integrated genome-wide association studies (GWASs) and T2D cell/tissue-specific histone modification ChIP-seq data to identify T2D-associated SNPs in super enhancer, followed by comprehensive bioinformatics analyses to further explore the functional importance of these SNPs. We identified several interesting T2D super enhancer SNPs. Interesting, most of them were clustered within the same or neighboring super enhancers. A number of SNPs are involved in chromatin interactive regulation and/or potentially influence the binding affinity of transcription factors. Gene Ontology (GO) analysis showed a significant enrichment in several well-known signaling pathways and regulatory process, e.g. WNT signaling pathway, which plays a key role in T2D metabolism. Our results highlighted the potential functional importance of T2D super enhancer SNPs, which may yield novel insights into the pathogenesis of T2D.

Diabetes Drugs Against Alzheimer’s Disease

Some findings of interest, relevant sections:

Studies in a mouse model of Alzheimer’s disease (AD) have shown how a drug that was originally developed to treat diabetes demonstrates what researchers in the U.K. and China call “clear promise” as a treatment for AD and other neurodegenerative disorders in humans. The studies, led by Christian Hölscher, Ph.D., at the U.K.’s Lancaster University, confirmed that AD mice treated using a triple-receptor agonist (TA) showed “significantly reversed memory loss,” as well as reduced neuroinflammation and oxidative stress, lower amyloid plaque load in the brain, and increased levels of brain-derived neurotropic factor (BDNF), a key growth factor that protects synaptic function… 

…Type 2 diabetes mellitus (T2DM) is a known risk factor for AD, and this association has motivated scientists to investigate whether antidiabetic drugs might also be effective against AD. Studies have shown that the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which have antidiabetic properties, can play a neuroprotective role in the brain and have demonstrated promising effects in animal models of AD. 

  Prof. Holscher’s team turned to a triple-receptor agonist that activates GIP-1, GIP, and glucagon receptors…The results showed that a daily injection of TA reversed memory loss in AD mice, which was assessed in a spatial water maze test. The drug also reduced levels of the mitochondrial proapoptotic signaling molecule BAX, increased the antiapoptotic signaling molecule Bcl-2, and boosted levels of BDNF. Levels of synaptophysin were also elevated, which the researchers say demonstrates protection against the synaptic loss that is seen in AD…

 

 …“Furthermore, TA treatment reduced the total amount of β-amyloid, reduced neuroinflammation (activated microglia and astrocytes), and oxidative stress in the cortex and hippocampus,” the authors write. “The results demonstrate for the first time that the novel GLP-1/GIP/Gcg receptor agonist has clear neuroprotective effects in the APP/PS1 mouse model of AD.” 

Given the “impressive” preclinical data demonstrating the neuroprotective properties of GLP-1, GIP, and glucagon receptor agonists, clinical trials are now under way to investigate the neuroprotective effects of the GLP-1 receptor agonists extendin-4 (Byetta®, Bydureon®) and liraglutide (Victoza®) in patients with AD or with Parkinson's disease, the authors note. “A pilot study testing the GLP-1 analogue liraglutide in AD patients showed promising results.”

That sounds like a very promising advance in the field of Alzheimer’s therapy, and also underscores the relationship between that disease and metabolic disorders.

Circular RNA, Type 2 Diabetes, And Depression

Production of circular RNA.  By Helixitta - Own work, created for Biology week #3, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=56444195

There is a link between type 2 diabetes and depression; expression of circular RNAs (unusual RNAs that are in circular rather than normal linear form and are therefore more stable and may affect gene expression differently) may be mechanistically linked to this association. Abstract:

Type 2 diabetes mellitus (T2DM) is closely related to depression; however, the exact molecular mechanisms of this association are unknown. Here, we investigated whether circular RNAs (circRNAs) in the blood are related to the occurrence of depression in patients with T2DM. Fourteen patients with T2DM and depressive symptoms, as assessed by the Self-Rating Depression Scale, were included in this study. Cutoff points of 44 (total coarse points) and 55 (standard score) were used to define depression. The Patient Health Questionnaire 9 was used for common mental disorders, and a score of 5 or more the cutoff for depression. Microarray assays and quantitative real-time reverse transcription polymerase chain reaction showed that 183 hsa-circRNAs were significantly upregulated, whereas 64 were downregulated in the T2DM with depression group (p < 0.05) compared with that in the T2DM group. Differentially expressed hsa-circRNAs could interact with microRNAs to target mRNA expression. KEGG pathway analysis predicted that upregulation of hsa-circRNA_003251, hsa-circRNA_015115, hsa-circRNA_100918, and hsa_circRNA_001520 may participate in the thyroid hormone, Wnt, ErbB, and mitogen-activated protein kinase signalling pathways. We speculate that differentially expressed hsa-circRNAs could help us to clarify the pathogenesis of depression in patients with T2DM and could represent novel molecular targets for clinical diagnosis and therapy.

Type I Diabetes: The Gut Microbiota Connection

By Mikael Häggström.When using this image in external works, it may be cited as:Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.orBy Mikael Häggström, used with permission. - See above. All used images are in public domain., Public Domain, https://commons.wikimedia.org/w/index.php?curid=6055517

The connection between gut microbiota and type 2 diabetes is known, and makes sense, as the long-term effects of the microbiota on the GI tract, food processing, secretion of factors inflammation, etc. can reasonably be seen as contributing to metabolic syndrome, insulin resistance, and, eventually, full-fledged type 2 diabetes. What is less well known is the link between intestinal bacteria and type 1 diabetes.  A review article has looked into this and concluded that two mechanisms may link the gut microbiota to type 1 diabetes.  First, if the infant has its GI tract colonized by sup-optimal bacteria, this will negatively affect the “education” of the immune system, resulting in a child vulnerable to immune system related diseases (e.g., autoimmune problems), including type 1 diabetes.  Note that type 1 diabetes results from autoimmune destruction if insulin-producing cells of the pancreases; therefore, an immune system not properly “trained” to distinguish “self” from “non-self” is “primed” to possibly result in attack against the targeted pancreatic cells.  Second, thus vulnerability, this predisposition, then develops into actual diabetes through the development of the antibodies that attack the pancreatic cells, and this development is associated with decreased diversity of the bacterial population of the gut, accompanied by an increase of certain bacterial species.  Protection against type 1 diabetes may therefore include modulating the colonization of the young intestinal tract to promote those bacterial species that would assist in normal immune function.  Abstract.

PURPOSE OF REVIEW:

The purpose of this review is to summarize potential modulations of the intestinal microbiome aimed at preventing or delaying progression to overt type 1 diabetes in the light of recently identified perturbations of the gut microbiota associated with the development of type 1 diabetes.

RECENT FINDINGS:

Accumulated data suggest that the gut microbiota is involved at two different steps in the evolution of type 1 diabetes. At the first step, the intestinal tract is colonized by a microbial community unable to provide an adequate education of the immune system. As a consequence, the infant acquires susceptibility to immune-mediated diseases, type 1 diabetes included. At the other step, the young child seroconverts to positivity for diabetes-associated autoantibodies. This is preceded or accompanied by a decrease in the diversity of the intestinal microbiota and an increased abundance of Bacteroides species. These changes will affect the disease process promoting progression toward overt type 1 diabetes. By providing specific probiotics, one can affect the colonization of the intestinal tract in the newborn infant or strengthen the immune education in early life. Human milk oligosaccharides function as nutrients for "healthy" bacteria. Dietary interventions applying modified starches can influence the numbers and activities of both autoreactive and regulatory T cells and provide protection against autoimmune diabetes in non-obese diabetic mice. Modulation of the intestinal microbiome holds the promise of effective protection against human type 1 diabetes.

Vitamin D And Type 2 Diabetes

By Sbrools - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2067061

Evidence linked here that vitamin D supplementation may help improve symptoms in type 2 diabetes patients.  Abstract:

BACKGROUND:Type 2 diabetes is a global health concern, with an increased prevalence and high cost of treatment.OBJECTIVE:The aim of this systematic review and meta-analysis was to determine the effect of vitamin D supplementation and improved vitamin D status on glycemia and insulin resistance in type 2 diabetic patients.DATA SOURCE:We searched PUBMED/Medline, Cumulative Index to Nursing and Allied Health, and Cochrane Library (until January 2017).STUDY SELECTION:Prospective clinical trials were selected evaluating the impact of vitamin D supplementation on glycosylated hemoglobin (HbA1c), serum fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) in diabetic patients.DATA EXTRACTION AND SYNTHESIS:We used a random-effects model to synthesize quantitative data, followed by a leave-one-out method for sensitivity analysis. The systematic review registration was CRD42017059555. From a total of 844 entries identified via literature search, 24 controlled trials (1528 individuals diagnosed with type 2 diabetes) were included. The meta-analysis indicated a significant reduction in HbA1c [mean difference: -0.30%; 95% confidence interval (CI): -0.45 to -0.15, P < 0.001], FPG [mean difference: -4.9 mg/dL (-0.27 mmol/L); 95% CI: -8.1 to -1.6 (-0.45 to -0.09 mmol/L), P = 0.003], and HOMA-IR (mean difference: -0.66; 95% CI: -1.06 to -0.26, P = 0.001) following vitamin D supplementation and significant increase in serum 25-hydroxyvitamin D levels [overall increase of 17 ± 2.4 ng/mL (42 ± 6 nmol/L)].CONCLUSIONS:Vitamin D supplementation, a minimum dose of 100 µg/d (4000 IU/d), may significantly reduce serum FPG, HbA1c, and HOMA-IR index, and helps to control glycemic response and improve insulin sensitivity in type 2 diabetic patients.

Insulin Analogs And Breast Cancer Risk

By Bakerstmd - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=39243250

Long-acting insulin analogs are used in the treatment of type 2 diabetes.  Given the possible effects of such drugs on cell signaling pathways, the cancer risk needs to be ascertained.  It has been shown that the drug glargine leads to increased risk of breast cancer for women with type 2 diabetes. Assuming various confounding variables were accounted for, this is a serious issue, and drug side effects always need to be considered when planning treatment.  Abstract:

Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in women with type 2 diabetes. Methods A population-based cohort of women 40 years or older, all of whom were treated with long-acting (glargine, detemir) or neutral protamine Hagedorn (NPH) insulin between 2002 and 2012, was formed using the United Kingdom's Clinical Practice Research Datalink. Women were followed until February 2015 or breast cancer diagnosis. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CIs of incident breast cancer, comparing long-acting insulin analogs with NPH overall, as well as by duration and cumulative dose. Results The cohort included 22,395 women who received insulin treatment, with 321 incident breast cancer events occurring during up to 12 years of follow-up (incidence rate 3.3 per 1,000 person-years). Compared with NPH insulin, insulin glargine was associated with an increased risk of breast cancer (HR, 1.44; 95% CI, 1.11 to 1.85), mainly increasing 5 years after glargine initiation (HR, 2.23; 95% CI, 1.32 to 3.77) and after > 30 prescriptions (HR, 2.29; 95% CI, 1.26 to 4.16). The risk was particularly elevated among prior insulin users (HR, 1.53; 95% CI, 1.10 to 2.12) but not for new users, which included fewer patients and for which one cannot rule out an HR of 1.81. The risk associated with insulin detemir was not significantly elevated (HR, 1.17; 95% CI, 0.77 to 1.77). Conclusion Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with type 2 diabetes. The risk associated with insulin detemir remains uncertain because there are fewer users of this insulin.

Dairy And Type 2 Diabetes

By Stefan Kühn - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=23754

There has been conflicting data with respect to whether dairy consumption affects risk for type 2 diabetes.  The study linked here suggests that the outcomes of dairy vs. diabetes depends on both the type of dairy consumed and the baseline glycemic status (normal, prediabetes, etc.) people have before changing their diets.  The conclusion:

Associations of dairy with incident prediabetes or diabetes varied both by dairy product and type and by baseline glycemic status in this middle-aged US population. Baseline glycemic status may partially underlie prior equivocal evidence regarding the role of dairy intake in diabetes.

Of course, dairy can have other effects besides diabetes.  It’s helpful (in general) for colon cancer and osteoporosis, but excessive dairy is a problem for prostate cancer.  High fat dairy may be helpful for diabetes, in some contexts, but poses a problem for other disorders. Then there is the problem of lactose intolerance for those who exhibit that.  I would suggest each person talks to their health care professional about that is best in their case and, always, to practice moderation. Too much of anything can be a problem.

Dried Fruit And Nuts For Type 2 Diabetes

Figure 1

Role of nutrients from nuts and dried fruits in glucose and insulin metabolism, and cellular and molecular mechanisms related to T2D/IR. CHO, carbohydrate; CMF, cellular membrane fluidity; GI, glycaemic index; IR, insulin resistance; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; T2D, type 2 diabetes. http://www.mdpi.com/2072-6643/9/7/673/htm (Figure from the open access paper)

Of course, diabetics need to follow the instructions of their physicians; however, we present this article for readers' interest.  It suggests that eating nuts and dried fruit (DF) can be beneficial for diabetics; some of the possible mechanisms are outlined in the figure (above) from the paper.  The fiber and relatively low glycemic index, healthy fats, minerals, and various bioactive compounds alter gene expression, microRNAs (RNA that control gene expression), and microbiota and so helpfully "modulate glucose and insulin metabolism." From the conclusion:

Undoubtedly, the specific composition of nuts and dried fruits means that they can be used to efficiently counteract metabolic diseases such as type 2 diabetes. Their unique profile of macronutrients, micronutrients and other bioactive compounds may explain the beneficial effects observed in clinical and epidemiological studies. However, the exact mechanisms by which they modulate glucose and insulin metabolism and influence T2D have yet to be fully discovered. They contain fiber, fat, minerals and other bioactive molecules that modulate several gene mechanisms at the cellular and molecular level. This may explain some of their beneficial effects. However, further basic and translational research is needed in order to extend their positive health benefits and to find novel mechanisms and targets to explain their contribution to the management of type 2 diabetes.

What about the sugars in the dried fruit?  The authors claim:

Carbohydrate Content—Glycaemic Index of Nuts and Dried Fruits

It should be noted that nuts are relatively low in CHO (approximately 15% of the total energy) whereas DFs have a high amount of CHO (60–80%). Nuts have a low glycaemic index and therefore increase the blood glucose level less and require less insulin secretion, thus favoring the control of T2D. However, because DFs are high in carbohydrates and fiber, their specific GI has been the object of considerable study. The GI of raisins was first evaluated in three heterogeneous groups of subjects (aerobically trained, sedentary or pre-diabetic) and was described between 49 and 69, therefore corresponding to the low-to-moderate GI foods [110]. However, later studies have reported that raisins are in the low GI category in healthy subjects (a GI of 49.4 and an insulinemic index of 47.1) [15]. This suggests a favorable postprandial glucose and insulin response [112], that could be explained by the high proportion of fructose that DFs contain.

Overall, the inclusion of both nuts and DFs in a balanced diet may reduce the overall glycaemic index of the diet, with benefits to glycaemic and insulinemic control in both healthy and T2D subjects.

Fructose of course can cause problems but when combined with the high fiber in the dried fruits that is obviated.

Diet Vs. Drugs

In general, I believe that, when and where appropriate, lifestyle changes should be tried first before taking drugs to deal with certain common types of chronic metabolic disorders (but of course always consult with your physician, as "in general" does not apply to every specific case). The experts agree with my opinion:

Many Americans, when faced with a serious health risk like high cholesterol, opt to take a pill rather than adopt healthier living habits.

A middle-aged woman I know is typifies this attitude. Thrilled with how well medication has controlled her rising cholesterol level, she continues to indulge in foods rich in cholesterol-raising saturated fats. She also carries around more body fat, especially risky abdominal fat, than is considered healthful.

I met people like that. For example, some people with Type II Diabetes believe that taking medication gives them green light to load up with cookies, cakes, and doughnuts.

Dr. Philip Greenland, a cardiologist and epidemiologist at Northwestern University Feinberg School of Medicine, said, “People should be following a heart-healthy diet, keeping their weight under control and exercising regularly. This would be a highly preferable approach. Unfortunately, it’s not the direction we’re going in.”

Admittedly, swallowing a little pill every day is simpler than changing one’s behaviors — and especially one’s eating habits. Yet experts like Dr. Greenland say that even when taking a statin or some other cholesterol-lowering drug, changes in diet and exercise habits are needed to maximize the drug’s benefits. He and others insist that drugs should be a last resort, after lifestyle changes fail to lower serum cholesterol adequately.

I agree. Unfortunately, Dr. Greenland is correct that this is not the direction we are going on. Everything and everyone needs to be medicated, it seems. I recently read a suggestion stating that drugs for treating the consequences of obesity are needed, since it is unrealistic to think people are going to lose weight. In other words, eat excessively, be obese, and then take a pill to try and evade the consequences. Of course, all of these drugs have side effects.  Wouldn’t it be easier to attack the problem rather than its consequences?  Lifestyle changes involving diet and exercise may help the underlying problem, and do so without expensive medications and their side-effects.

Noting that “every food a person might eat either fights or contributes to disease,” Dr. Kopecky said his clinic “tries to get everyone on a Mediterranean diet,” the traditional eating habits of people living in Greece and southern Italy. In addition to its heart benefits, studies suggest the Mediterranean diet may “reduce the risk of Alzheimer’s disease, cancer, Parkinson’s disease, diabetes, arthritis and the metabolic syndrome”… “people in Greece eat an average of nine servings a day of antioxidant-rich fruits and vegetables,” and the booklet outlines a long list of potentially healthful foods. Some examples include prunes, blueberries, red grapes, oranges, strawberries, kale, spinach, brussels sprouts, broccoli, beets, red bell peppers, corn and eggplant.

At a minimum, Americans should strive to consume two or more servings of vegetables and two to three or more servings of fresh fruit each day. If “fresh” is not available, “fresh frozen” is the next best option.

Living near the sea, Mediterraneans eat lots of seafood, often daily, and the Mayo diet recommends three or more servings a week of fish or shellfish. One or more servings should be a fatty fish rich in protective fish oils, like salmon, tuna, bluefish, sardines, mackerel and trout.

The white meat of chicken or turkey, eaten without the skin, is the land animal protein of choice, the Mayo Clinic says, with a serving size limited to 3 ounces of cooked meat, about the size of a deck of cards.

Unlike many Americans, people living along the Mediterranean also consume lots of foods with vegetable protein: legumes like split peas, lentils and peanuts, and beans like lima, black, red, kidney and navy…Whole grain breads and cereals are part of the recommended diet, but note that a serving of bread is one slice. Breads should be eaten plain or dipped in olive oil, the Mayo booklet says.

Which brings us back to fats. Olive oil, especially extra-virgin and virgin, the least processed forms, or canola oil should be used in place of butter or margarine…Eggs are back in fashion, consumed in moderation. That means a limit of three to four egg yolks a week, though no limit on egg whites. A good trick when preparing an omelet or scrambled eggs is to use two egg whites for every one yolk…However, red and processed meats should be limited to one three-ounce serving a week. And those cherished treats and desserts — pastries, cakes, doughnuts, cookies, pudding, French fries, potato chips and all sweetened and diet carbonated soft drinks — are best avoided altogether…Likewise, avoid high-fat dairy products…

Of course, what you eat is only half of the health-saving story. Regular physical exercise is a critical ingredient, even if it doesn’t result in weight loss. “Fitness trumps fatness,” Dr. Kopecky said, adding that being fit even while remaining fat markedly reduces cardiovascular risk. He urges parents to establish heart-healthy habits early in their children’s lives. “Patterns for physical activity are set by ages 6 to 9, and healthy eating habits by ages 9 to 12; together, they can result in a much lower risk for developing heart disease as adults,” he said.

This is all sound advice. If radical changes are considered too difficult at first, then go slowly. Reduce rather than eliminate the more unhealthy foods and continue to reduce their intake over time, until they are eliminated or are taken at a reasonable and acceptable frequency. Gradually increase your intake of fruits, vegetables, and whole grains. Increasingly incorporate physical activity into your daily regimen. Over time, you will have reached the required goals and objectives.

Eggs And Type 2 Diabetes

By David Benbennick - The egg is a Lucerne brand large grade AA, American. It is shown being cooked on a non-stick (probably Teflon) pan., Public Domain, https://commons.wikimedia.org/w/index.php?curid=43466

More recent dietary recommendations suggest that eating a moderate number of eggs in a healthy diet will not increase the risk of cardiovascular disease (CVD) in otherwise fit individuals.  What about individuals with type 2 diabetes or those at risk for that disease, unfortunately an ever-growing segment of the population in America and other Western nations?  This paper suggests that (from the abstract):

Results from randomized controlled trials suggest that consumption of 6 to 12 eggs per week, in the context of a diet that is consistent with guidelines on cardiovascular health promotion, has no adverse effect on major CVD risk factors in individuals at risk for developing diabetes or with type 2 diabetes. However, heterogeneities in study design, population included and interventions prevent firm conclusions from being drawn.

So, while more studies are needed, the data so far suggest moderate egg consumption might be fine for that segment of the population.  But, given that the conclusion is not definite, and given that every case is unique, readers should consult with their own physicians and/or nutritionists before making any change in their diet.  I personally eat mostly egg whites, but will eat some whole eggs from time to time (less than 6-12 per week).

Dementia in your 40s

Are you afraid of dementia? How about developing dementia in your 40s? You might be able to protect yourself ... by learning about the food for the brain.

By “food for the brain” I do not mean reading books and learning. True, challenging your brain is important based upon the “use it, or lose it” rule. However, in this post I am referring to the actual food you consume every day.

Do you eat lots of sugar? Have you been putting on pounds? Are you frequently tired? Are you moody most of the time? If you are not worried about your waistline and appearance, are you worried about succumbing to a dreadful illness due to your body weight?

Are you on the verge of being diagnosed with diabetes type 2? Or do you already have it? Do you have metabolic syndrome? Do you think that these conditions are not a problem because they could be controlled by medications?

I assure you that one body “malfunction” now would lead to another malfunction down the road, in your older years. If you escape cardiovascular diseases and cancer (both linked to overweight/obesity, metabolic syndrome, and insulin resistance), you may not be lucky to escape dementia associated with many different types of neurodegenerative diseases.

Both insulin resistance and diabetes are linked to several neurodegenerative diseases, including Alzheimer’s. Here is a source for more information.

In some neurodegenerative diseases, glucose is not properly used in the brain, and this situation is reminiscent of diabetes and insulin resistance. In fact, Alzheimer’s disease is sometimes called “type 3 diabetes”. And here is the bombshell: not only we may witness our children develop cancer before us, but we may also have to take care of our children when they develop dementia in their 40s:

"At a time in history when type 2 diabetes is diagnosed in progressively younger adults, the [new] findings have important implications for age of Alzheimer’s disease — with symptoms that will be increasingly reported by adults in their 50s and even possibly even in their 40s.”


Actionable
Stop eating sugar, stop drinking anything with sugar or sweeteners. Learn to read nutrition labels and recognize all 50+ names of sugar. Get the excess weight down.

And yes, mental exercise helps too:
You know what they say, use it or lose it. For a healthy brain functions, do these as described here:
· Challenge yourself
· Be socially active
· Follow a healthy diet
· Be physically active
· Reduce stress
· Protect your head
· Make healthy lifestyle choices
· Do your brain a favour - volunteer!