Scott Isaacs
@scottisaacsmd
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President-Elect @theaace , endocrinologist, obesity medicine, #MASLD , Emory Med School adjunct faculty. Posts are my own.
Atlanta, GA
Joined November 2010
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Physical activity is 1.5 times more effective at improving symptoms of depression, anxiety and distress compared to antidepressants.
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Physical inactivity is now recognized as the 4th
leading cause of death and is a contributor to 40 chronic diseases.
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More people lose weight when they exercise in the evening.
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Intermittent fasting is superior to caloric restriction for weight and visceral fat loss.
#IntermittentFasting
#VisceralFat
#MetabolicSyndrome
@ObesitySociety
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Taking metformin 30-60 minutes before a meal can significantly improve postprandial glucose control in individuals with type 2 diabetes. Timing matters!
#diabetes
#metformin
#glucosecontrol
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Changes that occur from down-regulation of GLUT4 in adipocytes in obesity and insulin resistance.
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Excellent review of the cardiovascular effects of exercise and the mechanisms involved.
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Exercise is superior to caloric restriction for visceral fat.
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The clinically most relevant mechanisms of action of GLP-1, glucagon, and GIP.
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Suboptimal sleep causes obesity and metabolic dysfunction.
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GLP-1 receptor agonists may help Alzheimer’s disease & Parkinson’s disease by reducing neuroinflammation through restoration of insulin signaling pathways, inducing neuroprotective effects.
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GLP-1 as the backbone of future obesity pharmacotherapy.
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All patients with type 2 diabetes should be screened for NAFLD/MASLD.
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Tirzepatide reduces both systolic and diastolic blood pressure, reduces total and LDL cholesterol levels, reduces triglycerides, and increases HDL cholesterol levels.
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GLP-1 medications are not associated with an increased risk of thyroid cancer.
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Regular exercise (e.g.,150 min/wk of walking) is 3.5 times more likely to achieve clinically meaningful liver fat reduction independent of weight loss. Exercise is not just for weight loss.
#NAFLD
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Exceedingly high HDL-C levels (>80 mg/dL in men and >100 mg/dL in women) increase the risk for cardiovascular events.
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All patients with type 2 diabetes should be screened for NAFLD/MASLD.
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Importance of 24-hour physical behaviors for type 2 diabetes.
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Cardiorenal mechanisms of action of GLP-1 RAs and SGLT2i.
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Anti-inflammatory and anti-diabetic effects of palmitic acid.
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Exercise even without weight loss improves multiple serum biomarkers of liver fibroinflammation in NAFLD/MASLD.
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There are significant reductions in HbA1c, BMI, and abdominal fat with intermittent fasting.
#intermittentfasting
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Insulin resistance is implicated in both the pathogenesis of
#MASLD
and its progression from steatosis to steatohepatitis, cirrhosis, and even hepatocellular carcinoma.
@ADA_Pubs
@AmDiabetesAssn
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Thyroid hormones regulate liver enzymes. When the liver is fatty, thyroid hormones don’t work right.
#HepaticHypothyroidism
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GLP-1 RAs reduce hepatic inflammation, steatosis, and fibrosis primarily through weight loss, as hepatocytes, Kupffer cells, and stellate cells do not express the canonical GLP-1R.
#NAFLD
@DanielJDrucker
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The ability of
#tirzepatide
and
#semaglutide
to melt weight away by tweaking biology gives credence to the idea that obesity is a disease.
#weightloss
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Once-daily oral semaglutide 50 mg reduced energy intake, lower appetite, and better control of eating, leading to significant weight loss compared with the placebo group.
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Exercise snacks (isolated ≤1-min bouts of vigorous exercise performed periodically throughout the day) alleviate the need for planning and allocating leisure time for structured exercise.
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Metabolically healthy obesity is a misleading term because it is associated with many chronic diseases and will eventually progress to metabolically unhealthy obesity.
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Study of
#semaglutide
vs
#tirzepatide
for weight loss. Tirzepide is the clear winner in terms of percentage of weight lost and number of participants who lost at least 10%.
@JAMAInternalMed
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This review discusses the use of
#metformin
beyond its traditional role in managing type 2 diabetes including PCOS, gestational diabetes, prediabetes, type 1 diabetes, cancer prevention, renal protection, Alzheimer's disease, and
#MASLD
.
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Obesity is a disorder of energy metabolism, in which there is low usable energy in the setting of elevated total energy. This leads to metabolic effects independent of excess energy while the excess energy drives weight gain.
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MASLD and MASH require urgent attention by primary care physicians and endocrinologists.
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Pharmacological approaches to
#MASLD
and
#MASH
.
@AmDiabetesAssn
#semaglutide
#tirzepatide
#pioglitazone
#SGLT2
#resmetirom
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Fast weight loss is better than slow weight loss. This study reaffirms that initial weight loss predicts long term success.
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New CVD Risk Calculator: SCORE2-Diabetes was validated to predict 10-year risk of CVD in patients with type 2
#diabetes
.
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Semaglutide 1.0 mg weekly is superior to liraglutide 3.0 mg daily for post-bariatric surgery weight loss.
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The FLOW trial:
#semaglutide
significantly reduces the risk of serious kidney outcomes, major cardiovascular events and death among people who have type 2 diabetes and chronic kidney disease.
#CKD
@NEJM
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I am proud to have coauthored this article on Endocrinology for the Hepatologist with my daughter Arabella Isaacs.
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This table of weight loss medications from
@TheAACE
2023 Type 2 Diabetes Management Algorithm summarizes therapies currently approved by the FDA, efficacy, dosing, delivery, potential side effects and contraindications.
#weightloss
#obesity
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When treating millions of people with GLP-1 medications like
#semaglutide
and
#tirzepatide
even relatively rare side effects will occur in a large number of people.
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This meta-analysis of 12 RCTs found that the effects of SGLT2 inhibitors on cardiovascular and kidney outcomes are consistent regardless of background use of GLP-1 RAs.
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Sleep deprivation causes insulin resistance, metabolic dysfunction and decreases fat oxidation.
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Alternate day fasting showed the highest effectiveness for weight loss in a meta-analysis comparing the effectiveness of alternate day fasting, the 5:2 diet, and time-restricted eating for weight loss.
#IntermittentFasting
#weightlossjourney
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Regular breakfast consumption and minimizing post-dinner snacking is critical for sustained weight loss.
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Impaired thyroid hormone conversion and increased rT3/T3 ratio in
#NAFLD
#NASH
comes from a predominance of deiodinase-3 over deiodinase-1 in an injured liver.
#livertwitter
#HepaticHypothyroidism
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This is everything you need to know about how to manage dyslipidemia in diabetes.
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Mechanisms of action and side effects of anti-obesity medications.
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Anti-obesity medication is important in managing obesity and type 2 diabetes, both before & after bariatric surgery.
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A summary of guidance for lipid management for primary and secondary prevention of cardiovascular disease from the NHS.
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Use of calcium supplements was associated with an increased risk of CVD events and all-cause mortality in people with diabetes.
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Calcium supplementation is associated with an increased risk of CVD events and all-cause mortality in people with diabetes, but not in those without diabetes.
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Patients with type 1 diabetes and obesity can benefit from type 2 diabetes medications SGLT2i and GLP1-RA to improve body weight and glucose levels.
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Most patients will benefit from having a primary weight-centric approach to diabetes treatment.
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Number 1 Top Cardiometabolic Story of 2023:
Phase 2 trial with
#retatrutide
, a GIP-GLP-1-GCG receptor triple agonist, resulted in a mean weight reduction of 24.2% after 48 weeks.
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GLP-1 medications (especially dulaglutide and semaglutide) are associated with reduced rates of nonfatal stroke and ischemic cerebrovascular events.
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Approaches for weight maintenance via energy expenditure & lean mass preservation. Targets include sympathetic nervous system, transient receptor potential channel activation, over browning of white adipose tissue & increased nonshivering thermogenesis.
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Tirzepatide has a greater A1c level and body weight reduction than semaglutide, particularly with the higher doses.
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Proposed NAFLD/MAFLD subtypes:
1⃣ Obesity subtype
2⃣ Metabolic unhealthy subtype
3�� Diabetes subtype
4⃣ Metabolic unhealthy non-diabetes subtype
5⃣ Obesity and diabetes subtype
6⃣ Metabolic unhealthy non-obesity subtype
7⃣ Mixed subtype
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Ultra-processed foods play a role in weight gain, the development of the metabolic syndrome and other chronic inflammatory diseases.
#Endotwitter
#Medtwitter
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Metabolically unhealthy people with a normal BMI and at least 1 component of the metabolic syndrome have 3 times higher risk of type 2 diabetes.
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Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
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Number 10 Top Cardiometabolic Story of 2023: Oral
#orforglipron
, a nonpeptide GLP-1 receptor agonist, was associated with -9.4% to -14.7% weight loss. Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists.
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Circadian disruptors (such as shift work, chronotype, sleep timing, sleep regularity, and meal timing) are detrimental to cardiometabolic health.
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Intermittent fasting works for poorly controlled insulin-treated type 2
#diabetes
by reducing total daily insulin dose and body weight.
#IntermittentFasting
#VisceralFat
#MetabolicSyndrome
@ADA_DiabetesPro
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The SELECT trial on semaglutide for weight loss in obesity without diabetes! Weight loss was sustained over 4 years, semaglutide led to weight loss of -10.2%, reduced waist circumference by -7.7 cm, and improved waist-to-height ratio by -6.9%.
#obesity
#weightloss
#semaglutide
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Is weight loss the (only) key to treat metabolic liver disease?
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The STRONG-D trial found that strength training was superior to aerobic training for improving glycemic control and increasing lean mass in people with type 2 diabetes.
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Tirzepatide and GLP-1 RA have demonstrated superiority in inducing weight loss and the ability to target multiple metabolic parameters (glycemic profile, lipid parameters, and blood pressure).
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Modified diagnostic criteria for steatotic liver disease proposed by the authors according to the latest
@AmerGastroAssn
Clinical Practice Update Expert Review.
@DrLoomba
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Alternate day fasting combined with aerobic exercise can decrease hepatic steatosis, body weight, fat mass, waist circumference, and ALT levels and increase insulin sensitivity.
#NAFLD
#LiverTwitter
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A low-carb diet boosts natural GLP-1 and GIP and lowers ghrelin levels when compared with a low-fat diet.
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This is an excellent article about the past, present, and future of the new wave of anti-obesity medications.
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Dapagliflozin significantly decreases liver fat content and pancreatic fat content in patients with type 2 diabetes and NAFLD/MASLD.
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People with PCOS have a higher risk of type 2 diabetes, hypertension, hepatocellular carcinoma, and depression or anxiety compared with controls. They also have a higher risk for cardiovascular disease, hepatic steatosis, and hepatic fibro-inflammation.
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