This document discusses the management of diabetes in patients with concomitant liver disease. It notes that about half of patients with cirrhosis have diabetes due to insulin resistance caused by the liver disease. Lifestyle changes and metformin are recommended initially if liver disease is mild. Insulin, sulfonylureas, meglitinides, alpha-glucosidase inhibitors, and thiazolidinediones may be used, with monitoring needed due to potential side effects or altered drug metabolism in liver disease. Insulin requirements can vary depending on the stage of liver disease.
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
Cardiovascular disease - more common in diabetic patients than in the general population
Dyslipidemia – common in patients with both types of diabetes.
Aggressive lipid treatment goals have been recommended for patients with type 2 diabetes
Diabetic Dyslipidemia is highly prevalent in the Indian diabetic population
Dyslipidemia in diabetes differs significantly with hypertriglyceridemia and small dense LDL-C
What is diabetes mellitus, Epidemiology of diabetes, Diabetes diagnosis, Features of diabetes, WHO classification of Diabetes Mellitus, Complications of diabetes, Metabolic alterations of diabetes, Oral glucose tolerance test, WHO criteria of OGTT interpretation, Classification of diabetes mellitus, Gestational diabetes, Pre-diabetes, Insulin, Biosynthesis of insulin, Insulin actions, Hypoglycemia, Impaired fasting glucose, Insulin structure
SIGNIFICANCE
OVERVIEW
WHAT IS DIABETES?
DEFINITION
MECHANISM
PREVELANCE
EPIDEMIOLOGY
CLASSIFICATION
GESTATIONAL DIABETES
RISK FACTORS
DIAGNOSIS
COMPLICATIONS
MEDICAL TEST
MEDICAL NUTRITIONAL THERAPY
HERBS FOR DIABETES
MYTHS AND FACTS
REFERENCES
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
Cardiovascular disease - more common in diabetic patients than in the general population
Dyslipidemia – common in patients with both types of diabetes.
Aggressive lipid treatment goals have been recommended for patients with type 2 diabetes
Diabetic Dyslipidemia is highly prevalent in the Indian diabetic population
Dyslipidemia in diabetes differs significantly with hypertriglyceridemia and small dense LDL-C
What is diabetes mellitus, Epidemiology of diabetes, Diabetes diagnosis, Features of diabetes, WHO classification of Diabetes Mellitus, Complications of diabetes, Metabolic alterations of diabetes, Oral glucose tolerance test, WHO criteria of OGTT interpretation, Classification of diabetes mellitus, Gestational diabetes, Pre-diabetes, Insulin, Biosynthesis of insulin, Insulin actions, Hypoglycemia, Impaired fasting glucose, Insulin structure
SIGNIFICANCE
OVERVIEW
WHAT IS DIABETES?
DEFINITION
MECHANISM
PREVELANCE
EPIDEMIOLOGY
CLASSIFICATION
GESTATIONAL DIABETES
RISK FACTORS
DIAGNOSIS
COMPLICATIONS
MEDICAL TEST
MEDICAL NUTRITIONAL THERAPY
HERBS FOR DIABETES
MYTHS AND FACTS
REFERENCES
Clinical, laboratory and histological associations in clinical, laboratory an...Dr. sreeremya S
Clinical, laboratory and histological associations in clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease
Diabetic nephropathy considered one of the most common complications of DM. This presentation answer the question are some diabetic patient immune to diabetic nephroapthy
Abstract— Non Alcoholic Fatty Liver Disease is also becoming public health impotance nowadays. So this study was aimed to determine the association of Non Alcoholic Fatty Liver Disease with metabolic syndrome and Cardio-Vascular disease along with assessment of degree of severity of NAFLD with respect to number of components of metabolic syndrome. This study includes a total of 222 subjects were enrolled as per the inclusion/exclusion criteria, out of which 110 cases who had NAFLD with hepatic steatosis on ultrasonography and 112 subjects who did not have NAFLD were considered control. These cases and controls were interrogated and investigated further. Observations were recorded and association of Non Alcoholic Fatty Liver Disease with metabolic syndrome and Cardio-Vascular disease along with assessment of degree of severity of NAFLD with respect to number of components of metabolic syndrome. Statistical methods used were unpaired student’s t-test for continuous variables, Fischer’s and chi-sq test for categorical variables using bivariate analysis by Graph Pad Instat Version 3.10. Risk was assessed in terms of Odd's Ratio. The patients with MS and NAFLD had a higher proportion of CVD compared with those who did not have NAFLD (29.1 vs 18.1 %). This study concludes that NAFLD is significantly associated with MS; most significant with WC, followed by TG and FBS and thus can be considered as hepatic component of MS. This needs more research with large multi-centric prospective studies to evaluate NAFLD as an independent risk factor for CVD.
Mr. AH is a 70-year-old man who was diagnosed with T2DM 10 years ago. He was initially treated with lifestyle management and metformin.
3 years later, his doctors advised him to add long acting basal insulin analogue to metformin, reached to 40U/day .
Other current medical conditions include: hypertension, hypothyroidism, and mild osteoporosis without fracture history.
Current medications; Metformin 1000 mg bid, long acting basal insulin analogue 40U/day , Candesartan 16 mg qd, Alendronate 70 mg once weekly, Levothyroxine 100 mg qd.
Physical exam: BMI 26 kg/m2, BP 140/80 mmHg, otherwise unremarkable.
His current FPG 140 mg/dL and HbA1c 8.5%. Kidney and liver functions are normal.
Disturbances of piturtary adrenal gonadal axis in hemodialysis ptalaa wafa
The kidneys play an important role in hormonal management. Endocrine disorders are one of the most crucial elements of ‘uraemic syndrome’ which is underestimated and has not been fully examined.
In CRF, there are complex endocrinal disorders related to hypothalamus and pituitary functions, and their relations to adrenal and gonadal functions also as far as sex hormones and adipose tissue hormones .
There is a great need for more randomized clinical trials to evaluate new and old treatment approaches, with the goal of developing better evidence-based practice guidelines.
Anti thyroid therapy like carbimazol,methimazol and propylethoiuracil may affect liver through affection of liver cell and can lead to cholestasis or liver cell failure
Fasting Ramadan carry many hazards to diabetic need to fast. Uncontrolled patients have a liability to some dangerous complications like DKA,HYPOGLYCEMIA,HHS AND thromboembolism
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
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The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
1. 1
Diabetes & liver
(Updates)
Alaa Wafa , MD.
Associate Professor of Internal Medicine
PGDIP DM Cardiff University UK
Diabetes & Endocrine Unit.
Mansoura University
2. AgendaAgenda
Magnitude of the problem
Spectrum of liver disease in type 2 diabetesSpectrum of liver disease in type 2 diabetes
Management of diabetes in patients withManagement of diabetes in patients with
concomitant liver disease.concomitant liver disease.
Management of liver disease in patients withManagement of liver disease in patients with
type 2 diabetes.type 2 diabetes.
5. Almost half of all
people with diabetes
live in just three
countries
China
India
USA
IDF
2013
6. Diabetes & Liver disease
Both problems have an important
interaction considering etiology & the
presence of any problem of each affect
the management of the other.
7. Spectrum of liver disease inSpectrum of liver disease in
type 2 diabetestype 2 diabetes
8. Spectrum of liver disease in type 2Spectrum of liver disease in type 2
diabetesdiabetes
1. Abnormal liver enzymes
1.Elevation of (ALT),, is common in patients with type 2
diabetes ( 24%)( 24%).
2.Evaluation of asymptomatic individuals with mild
elevations of ALT and AST reveals that 98% have liver
disease most commonly, fatty liver disease and
chronic hepatitis
Belcher G, Schernthaner G: Changes in liver tests during 1-year treatment of patients with type 2
diabetes with pioglitazone, metformin or gliclazide. Diabet Med 22:973–979, 2005
9.
10. Spectrum of liver disease in type 2 diabetesSpectrum of liver disease in type 2 diabetes
2. Non alcoholic fatty liver disease (NAFLD)
• It is defined as fatty liver disease in the absence of 20 g
alcohol/day.
• NAFLD consists of a spectrum of liver disease from
steatosis (fatty infiltration of the liver) to nonalcoholic
steatohepatitis (NASH), which consists of steatosis plus
inflammation, necrosis, and fibrosis.
• The prevalence of NAFLD in diabetes is estimated at 34–34–
74%74% and, in diabetes with obesity, at virtually 100%100%.
Pinto HC, et al: Nonalcoholic steatohepatitis: clinicopathological comparison with alcoholic hepatitis in
ambulatory and hospitalized patients. Dig Dis Sci 41:172–179, 1996
11. High prevalence of NAFLD* in Patients with
T2DM and Normal Plasma AST/ALT Levels
0
20
40
60
80
100
Non-obese Obese
Prevalence(%)
n=103
*Screened by the gold standard magnetic resonance and spectroscopy
(Portillo et al, submitted)
12.
13. Prevalence of NAFLD in predominantly obese patient with
or without T2DM according to different diagnostic tools
18. Spectrum of liver disease in type 2 diabetesSpectrum of liver disease in type 2 diabetes
3. Non alcoholic Steatohepatitis (NASH)
• While once considered a benign process, NASH has
been found to lead to cirrhosis and, in some cases, to
hepatocellular carcinoma.
• Of patients with NAFLD, 50% have NASH50% have NASH and 19% have19% have
cirrhosiscirrhosis at the time of diagnosis.
• Pathogenesis of steatosis :Insulin resistance resulting
in lipolysis, which increases circulating free fatty acids,
which are then taken up by the liver as an energy
source.
• The fatty acids overload the hepatic mitochondrial
oxidation system, leading to accumulation of fatty
acids in the liver.
Marchesini G, et al: Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37:917–923, 2003
19. Red Flags for NASH
• Age
• Gender
• Hispanic
• HTN
• Obesity
• Diabetes
• ALT and AST level
• AST/ALT ratio
• Insulin level
• PNPLA3
Non lab test or imaging
study will be able predict
with 100% accurancy
For me, the more risk
factors .. The more
concerned I become
20. Natural history of NASH
NASHNASH
CirrhosisCirrhosis
Liver deathLiver death
FibrosisFibrosis
Liver
transplant
Liver
transplant
HCC
15-20%40-50%
2-3%/yr
30-40%
2-12% of US population Risk of death in NASH
1st
CVD
2nd
Cancer
3rd
Liver
• Currently, liver biopsy is the
only way to diagnose NASH
• Liver biopsy is classify such
as large population
• Impractical
• Expensive
• Invasive
• Variability
• Need for clinical predication
rules and novel biomarker of
NASH
21. Types of biomarkers
• Moacular
– Genomic
– Proteomic
• CK-18
• ELF
• HA RBP-4
• IU panel
• Younossi panel
– Lipiomic
• Oxidized FA
• Non HDL cholesterol
• Small dense LDL
– Metabolomic
– Hydrid panels
• NAFIC panel
• Imaging
– MR - based
• MRI-PDFF
• MRS
• MRE
• Diffusion-weighted
imaging
– ultrasound
• USG
• Transient USG
• ARFI
– CT
22. Spectrum of liver disease in type 2 diabetes
4. Hepatitis C in diabetes
Recent study shows that insulin resistance is a
risk factor for esophageal varicesrisk factor for esophageal varices in hepatitis C
virus cirrhosis.
Recent studies suggest that the core protein of
HCV impairs insulin receptor substrate signaling,
which plays an important role in the metabolic
effects of insulin.
Cammà C, et al. Insulin resistance is a risk factor for esophageal varices in hepatitis C virus cirrhosis. Hepatology.
2009;49(1):195-203
23. Insulin Resistance and Hepatitis
• HCV infection contributes development of IR and
• Increase risk of development of T2DM
• Insulin resistance prevalence in CHC:
• 32% - 70%
• Insulin resistance associated with:
• Viral load
• fibrosis
24. Association of insulin resistance and
fibrosis progression
• IR associated with
moderate to serve
inflammation.
• HOMA increased
significantly with
fibrosis stage (p=0.001)
by logistic regression,
IR independently
associated with
significant fibrosis 0
3
6
9
12
15
Fibrosis (METAVIR)
F0-F1 F2 F3 F4
HOMA-IR
Moucari et al, Gastroenterology 2008; 134:416-423
25. Good News
• HCV eradication rates are now 90% or greater even for
cirrhosis
• Sustained virologic response associated with
decreased rates of progression to decompensation.
• Future is very bright. Newer direct acting antiviral
expected this year will be:
- All oral
-Minimal side effects
-Cure rate more than 90%
ADA Scientific Sessions San francisco 2014
26. 5. Cirrhosis in diabetes
The association of cirrhosis and diabetes is
complicated by the fact that cirrhosis itself is
associated with insulin resistance.
Wanless IR, Lentz JS: Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of
risk factors. Hepatology 12:1106–1110, 1990
27. Etiology of liver cirrhosis most frequentlyEtiology of liver cirrhosis most frequently
associated with diabetes mellitusassociated with diabetes mellitus
28. Spectrum of liver disease in type 2 diabetesSpectrum of liver disease in type 2 diabetes
6. Hepatocellular carcinoma in diabetes
• Numerous studies have confirmed a four foldfour fold
increased prevalenceincreased prevalence of hepatocellular carcinoma
in patients with diabetes as well as an increased
prevalence of diabetes in patients with HCC.
• Patients with HCC and DM have a mortality riskmortality risk
higherhigher than patients with HCC without DM.
• In another study involving 160 patients suffering
from HCC, those who had DM had a 1-year
mortality rate higher than those patients without
DM. Additionally, they had more extensive disease.
El-Serag HB, et al: Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma.
Gastroenterology 126:460–468, 2004
29. Hepatocellular carcinoma association
with diabetes
Hepatocellular
carcinoma
Diabetes
2-4 fold
1) Increased risk persists after
stratifying for age, gender,
ethnicity, viral hepatitis, alcohol,
iron overload
2) Synergistic with alcohol and
viral hepatitis.
J Natl cancer Inst 1997; Lawson DH, QJ Med 1986; La Vecchia C, Intl J cancer 1997; HO, J Natl
cancer Inst 1996; Yuan J M, Cancer 2004; Davila J A, Gut 2005; Hasson M M ,Hepatology 2002
31. Management of diabetes in patients
with concomitant liver disease
• Few studies have evaluated what is the most effective
therapy for DM in cirrhotic patients and what is the
impact of treatment of DM on the clinical course of liver
disease.
• The treatment of DM of cirrhotic patients has particular
characteristics that make it different from type 2 DM
without liver disease:
(1) About half the patients have malnutrition
(2) When clinical DM is diagnosed, the patient has advanced liver
disease
(3) Most of the oral hypoglycemic agents are metabolized in the
liver
(4) Patients often have episodes of hypoglycemia.
32. Management of diabetes in patients
with concomitant liver disease
1. Lifestyle modification
• The initial treatment of patients suffering from
mild to moderate hyperglycemia and
compensated liver disease may be a lifestyle
change, since at this stage the insulin
resistance is a dominant factor.
• This may be compromised by poor nutritional
status and general health. More than 50% of
patients with severe liver disease are
malnourished.
Suzuki A, et al: Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J
Hepatol 43:1060–1066, 2005
33. Management of diabetes in patients
with concomitant liver disease
1. Lifestyle manifestation
• Low-glycemic, low-calorie diets with a weight loss of
1–2 kg/week1–2 kg/week seem reasonable.
• Physical exercise which improves insulin resistance
may not be an appropriate measure in patients with
active liver disease.
34. Management of diabetes in patients
with concomitant liver disease
2. Pharmacologic therapy:
• While there are theoretical concerns about
altered drug metabolism and hepatotoxicity,
only patients with evidence of liver failureonly patients with evidence of liver failure
such as ascites, coagulopathy, or
encephalopathy have altered drug
metabolism.
35. Management of diabetes in patients
with concomitant liver disease
A. Metformin:
• Metformin may be particularly useful in obese
patients in whom it may cause mild weight loss.
• It is relatively contraindicated in patients with
advanced liver disease or in drinkers because it may
predispose to lactic acidosis.
• Metformin has not been reported to cause
hepatotoxicity and has shown some benefit in
patients with NAFLD.
Nair S, et al: Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment
Pharmacol Ther 20:23–28, 2004
36. Management of diabetes in patients
with concomitant liver disease
B. Insulin secretagogues:
• Sulfonylureas are generally safe in patients with liver
disease but may not overcome the insulin resistance
and defects in insulin secretion seen in patients with
coexistent alcoholic liver disease and pancreatic
damage.
• Sulfonylureas with a short half-life such as glipizide or
glyburide are preferred in these patients.
• Patients with decompensated cirrhosis, may have a
reduced ability to counteract hypoglycemia, and thus,
the response to therapy should be monitored closely.
37. Management of diabetes in patients
with concomitant liver disease
B. Insulin secretagogues:
Clinical trials assessing the efficacy of
meglitinides in the treatment of patients with
liver disease have not been reported. The
pharmacokinetics and tolerability of
nateglinide in patients with cirrhosis is not
significantly different than in control subjects.
Repaglinide and nateglinide have not been
associated with hepatotoxicity.
38. Management of diabetes in patients
with concomitant liver disease
C. α-Glucosidase inhibitors:
• The α-glucosidase inhibitors may be
particularly useful in patients with liver disease
because they act directly on the
gastrointestinal tract to decrease carbohydrate
digestion and thus glucose absorption, thereby
decreasing postprandial hyperglycemia.
• There was also a reduction in blood ammonia
levels, which paralleled an increase in bowel
movement frequency.
39. Management of diabetes in patients
with concomitant liver disease
C. α-Glucosidase inhibitors:
It was speculated that the increased bowel
frequency favored the proliferation of saccharolytic
bacteria while reducing the proliferation of
proteolytic bacteria, resulting in a reduction in
intestinal ammonia production.
Acarbose frequently causes mild transient
elevations of ALT and, on rare occasions, severe
liver disease. While the labeling of acarbose has a
warning for patients with liver disease, it appears
to be safe and effective in patients with hepatic
encephalopathy and type 2 diabetes.
Gentile S, et al: A randomized controlled trial of acarbose in hepatic encephalopathy. Clin Gastroenterol
Hepatol 3:184 –191, 2005
40. Management of diabetes in patients
with concomitant liver disease
D. Thiazolidinediones (TZD):
• TZDs may be especially useful because they enhance
insulin sensitivity, the underlying defect in NAFLD.
• There has been concern about their potential
hepatotoxicity because of the experience with
troglitazone.
• However, in pre-approval clinical trials of rosiglitazone
and pioglitazone, threefold elevations of ALT were
seen with the same frequency for rosiglitazone
(0.26%), pioglitazone (0.2%), and placebo (0.2 and
0.25%).
Harrison S, et al: A double-blind, placebo-controlled trial of pioglitazone in the treatment of non-alcoholic
steatohepatitis (NASH). Gastroenterology 128 (Suppl 2):A681, 2005
41. Management of diabetes in patients
with concomitant liver disease
D. Thiazolidinediones (TZD):
• It is currently recommended that serum ALT
levels be evaluated before the initiation of
rosiglitzone and pioglitazone therapy and that
therapy not be initiated if there is evidence of
active liver disease or if the serum ALT level
exceeds 2.5 times .
• Monitoring is recommended periodically
thereafter as clinically indicated rather than
every 2 months as previously recommended.
42. Management of diabetes in patients
with concomitant liver disease
E. Insulin:
• Insulin treatment is frequently required in patients with
diabetes and liver disease. Insulin requirements, however,
may vary.
• In patients with decompensated liver disease, the
requirement may be decreased due to reduced capacity for
gluconeogenesis and reduced hepatic breakdown of insulin.
• However, patients with impaired hepatic function may have
an increased need for insulin due to insulin resistance.
• In patients with hepatic encephalopathy who require high-
carbohydrate diets, resulting in postprandial hyperglycemia,
rapid-acting insulin analogs may be particularly useful.
43. MANAGEMENT OF LIVER DISEASE INMANAGEMENT OF LIVER DISEASE IN
PATIENTS WITH TYPE 2 DIABETESPATIENTS WITH TYPE 2 DIABETES
44. MANAGEMENT OF LIVER DISEASE INMANAGEMENT OF LIVER DISEASE IN
PATIENTS WITH TYPE 2 DIABETESPATIENTS WITH TYPE 2 DIABETES
I. Abnormal liver function tests:
• All patients with type 2 diabetes should have an ALT
and AST test done as part of their initial evaluation.
• At least 95% of patients with a confirmed minor
elevation of ALT or AST have chronic liver disease
independent of the degree of elevation. Thus, it is
always necessary to obtain a specific diagnosis.
• The most likely etiologies of minor elevations of
ALT/AST are NAFLD, hepatitis C, hepatitis B, and
alcohol.
45. MANAGEMENT OF LIVER DISEASE INMANAGEMENT OF LIVER DISEASE IN
PATIENTS WITH TYPE 2 DIABETESPATIENTS WITH TYPE 2 DIABETES
II. Fatty liver disease
The diagnosis of NAFLD or NASH should be
suspected in any patient with type 2 diabetes,
especially if there are abnormal liver function tests.
It should be specifically looked for in all obese
patients with type 2 diabetes.
Ultrasound studies may reveal a diffuse increase in
echogenicity, so-called “bright” liver.
Most patients with NAFLD found incidentally or by
screening ultrasound have a normal ALT.
46. MANAGEMENT OF LIVER DISEASE INMANAGEMENT OF LIVER DISEASE IN
PATIENTS WITH TYPE 2 DIABETESPATIENTS WITH TYPE 2 DIABETES
Treatment of NAFLD:
Most patients do not need to be treated. Only
patients with biopsy-proved NASH or the risk
factors (reversed ALT/AST ratio,
hypertriglyceridemia & thrombocytopenia)
should be treated.
The treatment consists of measures to lose
weight as well as pharmacologic intervention.
47. MANAGEMENT OF LIVER DISEASE INMANAGEMENT OF LIVER DISEASE IN
PATIENTS WITH TYPE 2 DIABETESPATIENTS WITH TYPE 2 DIABETES
Treatment of NAFLD:
1. Exercise and weight reduction:
Weight loss and exercise, which enhance insulin
sensitivity and result in reduction of steatosis.
Rapid weight reduction, however, may increase
necrosis, inflammation, and fibrosis.
The ideal rate of weight loss is not known, but 1.5
kg/week has been recommended.
Recent studies have demonstrated that bariatric surgery
either improves or completely reverses steatosis in
patients with obesity with or without DM.
48. MANAGEMENT OF LIVER DISEASE INMANAGEMENT OF LIVER DISEASE IN
PATIENTS WITH TYPE 2 DIABETESPATIENTS WITH TYPE 2 DIABETES
Treatment of NAFLD:
2. Pharmacologic therapy
Pharmacologic therapy of NAFLD is evolving. While
many studies have shown improvement in steatosis.
There are neither long-term studies to determine
whether they alter the natural history of the disease
nor studies to indicate whether relapse occurs after
treatment withdrawal.
Gemfibrozil, vitamin E, metformin, betaine,
silymarine, pioglitazone, rosiglitazone, atorvastatin,
losartan, orlistat, and pentoxifylline have all been
tried and have all been shown in small trials to
improve liver enzymes.
49. MANAGEMENT OF LIVER DISEASE INMANAGEMENT OF LIVER DISEASE IN
PATIENTS WITH TYPE 2 DIABETESPATIENTS WITH TYPE 2 DIABETES
Pharmacologic therapy of NAFLD:
Given that insulin resistance is central to the
pathogenesis of NAFLD, insulin sensitizing agents
should have utility, and there is increasing evidence that
they do.
Metformin has shown mixed results in human trials with
some improvement in ALT but not in histology. At this
time, treatment with metformin is not recommended
outside of clinical trials.
Five studies using pioglitazone from 16 to 48 weeks have
been published. All have shown improvement in serum
ALT and most in histology.
Lutchman G, et al: Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic
steatohepatitis: relationship to histological improvement. Clin Gastroenterol Hepatol 4: 1048–1052, 2006
50.
51.
52. MANAGEMENT OF LIVER DISEASE INMANAGEMENT OF LIVER DISEASE IN
PATIENTS WITH TYPE 2 DIABETESPATIENTS WITH TYPE 2 DIABETES
Pharmacologic therapy of NAFLD:
Three prospective controlled studies using
ursodeoxycholic acid, which reduces apoptosis and
has cytoprotective properties, have been conducted.
The results have been mixed.
Statins may reduce hepatic fat content in patients with
hyperlipidemia and NASH.
Lindor K: Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized, placebo-
controlled study (Abstract). Gastroenterology 124 (Suppl.1):A336, 2003
Horlander J, Kwo P, Cummings O: Atorvastatin for the treatment of NASH. Gastroenterology 5:A-544 , 2001
53. MANAGEMENT OF LIVER DISEASE INMANAGEMENT OF LIVER DISEASE IN
PATIENTS WITH TYPE 2 DIABETESPATIENTS WITH TYPE 2 DIABETES
Pharmacologic therapy of NAFLD:
Oxidative stress has been shown to be important in the
pathogenesis of NASH. It seems reasonable, therefore, to
try therapy with antioxidants.
Pilot studies with vitamin E have been conducted with
promising results, but a meta-analysis of high-dose
vitamin E revealed an increase in overall mortality.
Pentoxifylline is a compound that inhibits TNF-α. It is used
in the treatment of alcoholic hepatitis. A pilot study has
shown improvement in liver enzymes in patients with
NASH. However, the high incidence of side effects led to
early withdrawal in many patients.
Miller ER, 3rd, et al: Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med
142:37– 46, 2005
55. Medical History and physical examMedical History and physical exam
AST/ALTAST/ALT
Liver
ultrasound
Liver
ultrasoundAssess risk of
NAFLD
Assess risk of
NAFLD
No farther
evaluation
Consider liver
ultrasound in
selected cases
Consider liver
ultrasound in
selected cases
Assess risk of
NAFLD
Assess risk of
NAFLD
Contemplate alternative
diagnostic tools (clinical models
biomarkers, alternative imaging
tests, etc.
Contemplate alternative
diagnostic tools (clinical models
biomarkers, alternative imaging
tests, etc.
Consider biopsyConsider biopsy
Recommend hepatology
referral to rule out other
cases of liver diseases
• Close flowing up
• Address lifestyle and
cv risk factors
NASHNo NASH
• Lifestyle intervention
• Consider pharmacological therapy
Abnormal
Normal
Rule out other
causes of
liver disease
Low riskHigh risk
NormalNAFLD
High risk
Low risk
NAFLD
Normal
Algorithm for the
Management of NAFLD
by Endocrinologistic
Recommend
Hepatology referral
Family history
T2DM ? Obesity?
Metabolic
Elevated
56. SummarySummary
Type 2 diabetes is associated with a large number of liver
disorders including elevated liver enzymes, fatty liver
disease, cirrhosis, hepatocellular carcinoma. In addition,
there is an unexplained association with HCV.
The presence of liver disease (unless decompensated)
has little implication for the specific treatment of diabetes,
and the presence of diabetes has little implication for the
specific treatment of liver disease.
Patients with decompensated liver disease are more
susceptible to hypoglycemia and require careful
monitoring.
There continues to be a need for long-term placebo
controlled trials for the treatment of NAFLD and for the
treatment of diabetes in patients with liver disease.