A 2021 issue of Diabetes Care reveals the shocking prevalence of advanced liver fibrosis (scarring) in folks with type 2 diabetes: one of every six. Fibrosis may eventually lead to cirrhosis and require a liver transplant. The study at hand used vibration-controlled transient elastography to measure liver stiffness. The more fibrosis, the stiffer the liver. The measuring device “uses a pulse-echo ultrasound technique to quantify the speed of mechanically induced shear wave within liver tissue,” which correlates with the severity of fibrosis. Liver fat, i.e., steatosis, can also be quantified at the same time by measuring the ultrasonic attenuation of the echo wave.
Here’s the study abstract:
Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM).
RESEARCH DESIGN AND METHODS
A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m2; and HbA1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.
The prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3–4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI).
Moderate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.
Retinopathy is a fancy word meaning disease of the retina, the light detecting membrane at the back of the eyeball. About two in five folks with diabetes have some form or degree of diabetic retinopathy. The pathology is mostly in the arterial blood vessels of the retina. Keeping blood sugars under good control is one way to prevent diabetic retinopathy. Once diagnosed, it can be treated with injections, lasers, or surgery.
Here’s the abstract from a recent scientific report the looked at the ocular effects of gastric bypass surgery in obese type 2 diabetics. Over the course of 4.5 years, the risk of diabetic retinopathy was 40% less in those who had bypass surgery.
Importance Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients.
Objective To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP.
Design, Setting, and Participants Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019.
Exposure Gastric bypass surgery.
Main Outcomes and Measures Incidence of new DR and other diabetic ocular complications.
Results The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6% (1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5% (1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P < .001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI.
Conclusions and Relevance This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment.
In the study at hand, frailty was measured by exhaustion, weakness, physical activity, walking speed, and weight loss. From the Journal of the American Medical Medical Directors Association way back in 2014:
Background and objective: Low intake of certain micronutrients and protein has been associated with higher risk of frailty. However, very few studies have assessed the effect of global dietary patterns on frailty. This study examined the association between adherence to the Mediterranean diet (MD) and the risk of frailty in older adults.
Design, setting, and participants: Prospective cohort study with 1815 community-dwelling individuals aged ≥60 years recruited in 2008-2010 in Spain.
Measurements: At baseline, the degree of MD [Mediterranean Diet] adherence was measured with the Mediterranean Diet Adherence Screener (MEDAS) score and the Mediterranean Diet Score, also known as the Trichopoulou index. In 2012, individuals were reassessed to detect incident frailty, defined as having at least 3 of the following criteria: exhaustion, muscle weakness, low physical activity, slow walking speed, and weight loss. The study associations were summarized with odds ratios (OR) and their 95% confidence interval (CI) obtained from logistic regression, with adjustment for the main confounders.
Results: Over a mean follow-up of 3.5 years, 137 persons with incident frailty were identified. Compared with individuals in the lowest tertile of the MEDAS score (lowest MD adherence), the OR (95% CI) of frailty was 0.85 (0.54-1.36) in those in the second tertile, and 0.65 (0.40-1.04; P for trend = .07) in the third tertile. Corresponding figures for the Mediterranean Diet Score were 0.59 (0.37-0.95) and 0.48 (0.30-0.77; P for trend = .002). Being in the highest tertile of MEDAS was associated with reduced risk of slow walking (OR 0.53; 95% CI 0.35-0.79) and of weight loss (OR 0.53; 95% CI 0.36-0.80). Lastly, the risk of frailty was inversely associated with consumption of fish (OR 0.66; 95% CI 0.45-0.97) and fruit (OR 0.59; 95% CI 0.39-0.91).
Conclusions: Among community-dwelling older adults, an increasing adherence to the MD was associated with decreasing risk of frailty.
Did you notice another good reason to eat fish?
I wonder why the research was published in the Journal of the American Medical Medical Directors Association?
The traditional Mediterranean diet has long been linked to lower risk of certain cancers, particularly colon, breast, uterus, and prostate cancer. That’s one reason the diets usually ranked as the #1 healthiest diet in the U.S. News and World Report’s annual diet survey. A new study of a Netherlands population suggest that the anti-cancer benefit applies only to women. From a 2020 issue of the Journal of the Academy of Nutrition and Dietetics:
In this NLCS analysis, sex-specific associations of a priori defined Mediterranean diet adherence with risks of overall cancer and cancer subgroups defined by relations with 3 major cancer risk factors (tobacco smoking, obesity, and alcohol consumption) were investigated. In women, middle compared with low aMEDr values [alternate Mediterranean diet score without alcohol] were significantly associated with a reduced risk of overall cancer and the majority of the cancer subgroups investigated. Other associations in women were not statistically significant after full adjustment for confounding, but all estimates were below 1. No association was observed between aMEDr and risk of overall cancer or any of the cancer subgroups in men. Inclusion of alcohol in the Mediterranean diet score diminished the model performance.
Even though the association of Mediterranean diet adherence with overall cancer risk is comprised of a combination of potentially diverging associations with individual cancer (sub)types, overall cancer risk is an interesting end point for epidemiological studies. It provides insight in the overall possible benefits of Mediterranean diet adherence and the potential of the Mediterranean diet as a dietary strategy for cancer prevention. Findings of previously conducted prospective studies evaluating the relation between a priori defined Mediterranean diet adherence and overall cancer risk have been inconclusive and were rarely specified by sex.
A priori defined Mediterranean diet adherence has previously significantly been associated with a reduced overall cancer risk in the total European Prospective Investigation into Cancer and Nutrition (EPIC) cohort as well as the Greek EPIC cohort.9,10 Comparing the highest with the lowest Mediterranean diet adherence category in the total EPIC cohort, HRs (95% CIs) of 0.93 (0.88-0.99) and 0.93 (0.89-0.96) were observed for men and women, respectively. Although inverse associations were also suggested for both sexes in the Greek EPIC cohort, only effect estimates obtained in women reached statistical significance (HRhigh vs low [95% CI]: 0.83 [0.63-1.09] for men and 0.73 [0.56-0.96] for women). In addition to the previously mentioned EPIC studies, weak inverse associations between Mediterranean diet adherence and overall cancer risk were observed in men (HRper tertile increase [95% CI]: 0.97 [0.94-1.01]) and women (HRper tertile increase [95% CI]: 0.97 [0.93-1.00]) participating in the Swedish prospective Västerbotten Intervention Programme. In the present analysis of the NLCS cohort, a priori defined Mediterranean diet adherence was not associated with overall cancer risk in men. In regard to women, although the multivariable-adjusted associations in female NLCS participants were not statistically significant in most cases, effect estimates were stronger inverse than those observed for women in the total EPIC cohort, which did reach statistical significance possibly due to the larger number of cases. Additional cohort studies in Germany and France have investigated the association between Mediterranean diet adherence and overall cancer risk in men and women together and did not observe an association. Besides the prospective cohort evidence, a reduced overall cancer risk (borderline significant, P = .05) was indicated in patients with coronary heart disease who followed an α-linolenic acid-rich Mediterranean-type diet as opposed to a control diet close to the step 1 prudent diet of the American Heart Association in the randomized Lyon Diet Heart Study. However, results should be interpreted with caution because they were based on only 24 incident cancer cases.
The title above sums it up. If you’re eating pasta frequently and trying to lose weight, you do have to be careful not to over-eat. In other words, you generally have to restrict calories. In the study at hand, I don’t know how many daily calories were allowed since I haven’t read the full report. Here’s the abstract:
Background & aims
The effect of pasta consumption within a low-energy [read: calorie-restricted] Mediterranean diet on body weight regulation has been scarcely explored. This paper investigates the effect of two Mediterranean diets, which differed for lower or higher pasta intake, on body weight change in individuals with obesity.
Methods & Results
Forty-nine volunteers finished a quasi-experimental 6-month two–parallel group dietary intervention. Participants were assigned to a low-energy high pasta (HP) or to a low-energy low Pasta (LP) group on the basis of their pasta intake (HP ≥ 5 or LP ≤ 3 times/week). Anthropometrics, blood pressure and heart rate were measured every month. Weight maintenance was checked at month 12. Body composition (bioelectrical impedance analysis, BIA), food intake (24-h recall plus a 7-day carbohydrate record) and the perceived quality of life (36-item short-form health survey, SF-36) were assessed at baseline, 3 and 6 months. Blood samples were collected at baseline and month 6 to assess glucose and lipid metabolism. After 6-month intervention, body weight reduction was −10 ± 8% and −7 ± 4% in HP and LP diet, respectively, and it remained similar at month 12. Both dietary interventions improved anthropometric parameters, body composition, glucose and lipid metabolism, but no significant differences were observed between treatment groups. No differences were observed for blood pressure and heart rate between treatments and among times. HP diet significantly improved perception of quality of life for the physical component.
Independent of pasta consumption frequency, low-energy Mediterranean diets were successful in improving anthropometrics, physiological parameters and dietary habits after a 6-month weight-loss intervention.
Mediterranean diet (MD) has been related to reduced overall mortality and improved diseases’ outcome. Purpose of our study was to estimate the impact of MD on duration of admission, financial cost and mortality (from hospitalization up to 24 months afterwards) in elderly, hospitalized patients.
Research Methods & Procedures:
One hundred eighty three elderly patients (aged >65 years), urgently admitted for any cause in the Internal Medicine department of our hospital, participated in this observational study. Duration of admission and its financial cost, mortality (during hospitalization, 6 and 24 months after discharge), physical activity, medical and anthropometric data were recorded and they were correlated with the level of adherence to MD (MedDiet score).
In multivariate analyses, duration of admission decreased 0.3 days for each unit increase of MedDiet score (p<0.0001), 2.1 days for each 1g/dL increase of albumin (p=0.001) and increased 0.1 days for each day of previous admissions (p<0.0001). Extended hospitalization (p<0.0001) and its interaction with MedDiet score (p=0.01) remained the significant associated variables for financial cost. Mortality risk increased 3% per each year increase of age (HR=1.03, p=0.02), 6% for each previous admission (HR=1.06, p=0.04) whereas it decreased 13% per each unit increase of MedDiet score (HR=0.87, p<0.0001).
Adoption of MD decreases duration of admission and long-term mortality in elderly hospitalized patients with parallel reduction of relevant financial cost.
Pro-inflammatory cytokines serve an important purpose, in marshaling the inflammatory response that fights off viruses, bacteria, and other pathogens. That’s the protective mechanism of inflammation at work. But for the pro-inflammatory cytokine response to be beneficial, it must be proportional to the threat. A too vigorous response of pro-inflammatory cytokines creates a dangerous amount of inflammation—and can actually serve to spread the viral infection, rather than tamping it down. It is this inflammatory overreaction and viral spread that appears to take place in the most serious cases of COVID-19.
I spent 10 minutes on the Internet trying to find the appropriate dose of melatonin for its possible preventative and treatment powers. But no luck. It’s likely in the range of 1 to 10 mg/day, typically taken at night or bedtime. For insomnia in my hospitalized patients, I start at 1.5 mg. Most of my colleagues use a much higher dose. Dr Josh Farkas at emcrit.org suggests that the treatment dose is 5 mg/day.
As always, check with your personal physician first.
Low-carbohydrate diets help many folks, but not all, lose excess fat weight. When low-carb diets help, it may be related to Total Energy Expenditure (TEE). When you read “energy,” think calories. TEE is a combination of calories needed for 1) basic life processes (i.e., basal metabolic rate, as needed to maintain heart beats, breathing, steady body heat, growth and repair of tissues, etc.), 2) processing of ingested food (dietary thermogenesis), and 3) physical exercise.
Here’s the abstract of an article in The Journal of Nutrition that examines the headline question. It’s complicated and I haven’t read the full study yet.
Many obesity experts believe that to lose excess fat weight, you have to ingest fewer calories than you burn on a daily basis for physical exercise and basal metabolic rate. This creates a calorie (energy) deficit. Your body satisfies that deficit by converting fat tissue to weightless energy. The authors of the study at hand are essentially saying that, after 2-3 weeks, a low-carb diet “revs up your metabolism” to burn more calories. That can help you lose weight or maintain weight loss, unless you over-eat.
Here you go, nutrition nerds:
The effect of macronutrient composition on total energy expenditure (TEE) remains controversial, with divergent findings among studies. One source of heterogeneity may be study duration, as physiological adaptation to lower carbohydrate intake may require 2 to 3 wk.
We tested the hypothesis that the effects of carbohydrate [expressed as % of energy intake (EI)] on TEE vary with time.
The sample included trials from a previous meta-analysis and new trials identified in a PubMed search through 9 March 2020 comparing lower- and higher-carbohydrate diets, controlled for EI or body weight. Three reviewers independently extracted data and reconciled discrepancies. Effects on TEE were pooled using inverse-variance-weighted meta-analysis, with between-study heterogeneity assessed using the I2 statistic. Meta-regression was used to quantify the influence of study duration, dichotomized at 2.5 wk.ResultsThe 29 trials ranged in duration from 1 to 140 d (median: 4 d) and included 617 participants. Difference in carbohydrate between intervention arms ranged from 8% to 77% EI (median: 30%). Compared with reported findings in the prior analysis (I2 = 32.2%), we found greater heterogeneity (I2 = 90.9% in the reanalysis, 81.6% in the updated analysis). Study duration modified the diet effect on TEE (P < 0.001). Among 23 shorter trials, TEE was reduced on lower-carbohydrate diets (−50.0 kcal/d; 95% CI: −77.4, −22.6 kcal/d) with substantial heterogeneity (I2 = 69.8). Among 6 longer trials, TEE was increased on low-carbohydrate diets (135.4 kcal/d; 95% CI: 72.0, 198.7 kcal/d) with low heterogeneity (I2 = 26.4). Expressed per 10% decrease in carbohydrate as %EI, the TEE effects in shorter and longer trials were −14.5 kcal/d and 50.4 kcal/d, respectively. Findings were materially unchanged in sensitivity analyses.
Lower-carbohydrate diets transiently reduce TEE, with a larger increase after ∼2.5 wk. These findings highlight the importance of longer trials to understand chronic macronutrient effects and suggest a mechanism whereby lower-carbohydrate diets may facilitate weight loss.
This finding supports a prediction of the carbohydrate-insulin model and suggests a mechanism whereby dietary carbohydrate reduction could aid in the prevention and treatment of obesity. According to this model, the high insulin-to-glucagon ratio with a diet high in glycemic load (mathematical product of glycemic index and carbohydrate amount) shifts the partitioning of metabolic fuels from oxidation in lean tissue to storage in adipose tissue. If the effects observed here persist over the long term, then reducing dietary carbohydrate intake by half from 60% of energy intake (a typical level for low-fat diets) would increase energy expenditure by ∼150 kcal/d, counterbalancing (if not compensated for by other factors) much of the secular increase in energy intake thought by some to underlie the obesity epidemic.
The clinical efficacy and utility of ivermectin in SARS CoV-2 infected patients are unpredictable at this stage, as we are dealing with a completely novel virus. However, repurposing existing drugs as possible COVID-19 treatment is astute usage of existing resources, and we await results of well-designed large scale randomized controlled clinical trials exploring treatment efficacy of ivermectin to treat SARS-CoV-2.
The authors of this letter mention current clinical trials (~38) with a dose [presumably by mouth] ranging from 200 to 1200 mcg/kg body weight, for a duration of 3–7 days, which is showing promising results both in terms of symptoms as well as viral load reduction. Another article mentioned the usual treatment dose is 0.2mg/kg on day 1 and day 3 followed by Days 6 and 8 if not recovered.
The authors cite the Broward Health hospital system study from South Florida. In this small pilot study, hospitalized patients treated with ivermectin had a better survival rate compared with “standard care,” whatever that was back in Spring 2020. The ivermectin-treated patients received “at least one dose” of the drug at 200 mcg/kg, by mouth. Has this report been peer-reviewed and published yet? If not, why not?
Another study: “Two-dose ivermectin prophylaxis at a dose of 300 μg/kg with a gap of 72 hours was associated 73% reduction of COVID-19 infection among [hospital] healthcare workers for the following one-month. Further research is required before its large scale use.”
A small study in Barcelona found no benefit from a single standard dose (200 mcg/kg) of ivermectin in patients hospitalized with severe disease. They suggest that a higher dose might be useful.
I’ve spent about 90 minutes on my day off trying to figure out if I should prescribe ivermectin to my hospitalized patients. My conclusion is that we need more and better data before it’s ready for prime time. I agree with Dr Ananda Swaminathan, who probably spent many hours more on the subject:
Evidence for the use of Ivermectin is based on in vitro [lab studies, not living animals], prophylaxis, clinical, safety, and large-scale epidemiologic studies (heterogenous populations in multiple different settings) BUT…
Many of the trials thus far are methodologically flawed without enough information about baseline demographics, multiple primary outcomes, soft/subjective outcomes, convenience samples, and unclear definitions, just to name a few
Additionally, a valid concern in evaluating the literature is that many of the trials have not yet passed the peer review process and are in pre-print format
Although Ivermectin is cheap, readily available, with a fairly safe side effect profile, based on the evaluation of the literature above, at this time, Ivermectin should not be recommended outside of a clinical trial to ensure we get a true answer of effect
Ivermectin is interesting, there is certainly signal to evaluate further, but in our desire to want a treatment option, let’s not continue to do the same thing over and over again, as we saw play out with Hydroxychloroquine
Like they say, “more studies are needed.”
Steve Parker, M.D.
PS: Something you can do to help prevent and survive COVID-19 is to get and stay as healthy as possible. Let me help: