Dr.

YAHYA ARABYAT
FAMILLY MEDICINE CONSULTANT

DIABTES,a common chronic and progressive cardiorenometabolic disorder,

due to impaired carbohydrate,protein,fat metabolism Characterized by
hyperglycemia resulting from variable degrees of insulin resistance and deficiency
It is a major cause of morbidity, disability and mortality worldwide.

1
Classifications of Diabetes
▪
Type 1 DM
Type 1 diabetes usually develops as a result of autoimmune pancreatic beta-cell destruction in
genetically susceptible individuals.
▪ Beta-cell destruction proceeds sub-clinically for months to years as insulinitis
▪ Through many phases
▪ Stag(1) presymptomatic islet autoimmunity,marked by the presence of two or more islet
autoantibodies
▪ Stage (2),characterized by persistent autoantibodies and glucose abnormalities
▪ Stage(3) ,with clinical onset of hyperglycemia and declining beta cell function.
▪ (inflammation of the beta cell). When 80% to 90% of beta cells have been destroyed,
hyperglycemia develops.
▪ Teblizumab recommended to delay onset of stage 3 in people aged 8 year with preclinical– (stage
2) T1DM(Standard of medical care).
▪ Insulin resistance has no role in the pathophysiology of type 1 diabetes.
▪ The onset of T1DM may be triggered by environmental factor such as viral or other infection.
 Type 1 DM
▪ Epidemiology
▪ Accounts for about 5% to 10% of all patients with diabetes. It is the most commonly
diagnosed diabetes of youth (under 20 years of age) and causes ≥85% of all diabetes cases in
this age group.

▪ There is significant geographic variation in the incidence of type 1 diabetes. It is more

common in Europeans and less common in Asians

▪ Incidence rates ranging from 0.1 per 100,000 per year in parts of China to 40.9 per 100,000
per year in Finland.
▪ The onset of T1DM is triggered by environmental factors such as viral or other infection
 Type 2 DM
▪ Often presents on a background genetic predisposition and is characterized by
insulin resistance and relative insulin deficiency.

▪ Insulin resistance is aggravated by ageing, being overweight/obesity.

▪ Insulin resistance affects primarily the liver, muscle, and adipocytes, and it is
characterized by complex derangements in cellular receptors, intracellular
glucose kinase function, and other intracellular metabolic processes.
 Epidemiology
The current prevalence of diabetes among adults is
10.5%worldwide(536.6million adults)with marked variation across
regions and countries and is estimated to reach 12,2%(783.2million
adult) by 2045.
Diabetes is more prevalent in high income (11.1%)and middle
income(10.8%)countries than in low income countries(5.5%).
The prevalence is rising everywhere rapidly in middle income
countries expected to reach 13.1% by 2045 probably because of
changing diet and life style factors ,rising rate of obesity inadequate
resources for early diagnosis
Data from low income countries are likly to be underestimated because
of barriers to screening and diagnosis.
:
Ref KarurangaS,et al IDF DIABETES ATLAS ,Diabetes Res.Clin Pract2022
 Gestational DM
▪ Products of the placenta, including tumor necrosis factor-alpha (TNF-alpha) and
human placental lactogen (HPL), are thought to play key roles in inducing
maternal insulin resistance.

▪ During normal pregnancy, resistance to insulin action increases. In most

pregnancies, pancreatic beta cells are able to compensate for increased insulin
demands, and normoglycaemia is maintained.

▪ GDM is most often recognized at 24 to 28 weeks of gestation, based on an

abnormal glucose tolerance test.
 Other types of DM
▪ Other causes like:
▪ monogenic diabetes syndromes
(such as neonatal diabetes and maturity-onset diabetes of the young (MODY)
Neonatal diabetes is diagnosed at less than six month of age(whatever their
age now)individual with neonatal diabetes have mutation in gene kcnj11
individual with this mutation can transfer from daily insulin to sulphonylurea
Because patient have lots of beta cells and they have insulin they just don,t
release it when blood sugar level goes up.
-Maturity onset diabetes(mody)is characterized by three features:
Young age of onset(at least one family member diagnosed below the age of 25)
-autosomal dominant inheritance
-noninsulin dependent diabetes (or evidence of endogenous insulin production
more than 3 years post diagnosis
 Monogenic Diabetes
Monogenic diabetes is diabetes caused by a change in a single gene. This can broadly be
separated into neonatal diabetes and maturity onset diabetes of the young.
Neonatal diabetes is diagnosed at less than six months of age(whatever their age now) .
Patients with neonatal diabetes have lots of beta cells and they have lots of insulin. They just
don't release it when the blood sugar level goes up. And because it was thought these children
had a type 1 diabetes, they were given insulin injections from birth. But now we knew that they
didn't need to have them and they could actually have sulfonylurea drugs.
Maturity onset diabetes of the young (MODY)
is characterised by three key features:
◦ a young age of onset (at least one family member diagnosed below the age of 25 years)
◦ autosomal dominant inheritance (diabetes passed down from an affected parent to their child, with
diabetes in 2 or more generations (test parents or grandparents)
◦ non insulin dependent diabetes (or evidence of endogenous insulin production more than 3 years post
diagnosis protein C level).
◦ Different types of MODY.

◦ GCK(GLUCOKINASE)MODY-mild hyperglycemia with fasting blood sugar 99-144mg/dl and

Hba1c5.8%-7.6% no need for treatment(reduced risk of complication).
◦ Transcriptional factors
◦ HNF1A MODY. Most common sensitive to low dose of sulphonylurea
◦ HNF4A MODY
◦ HNF1B MODY
 Clinical Manifestations
▪ Most patients are ASYMPTOMATIC!
Clinical Manifestations
 Risk Factors
▪ Physical inactivity

▪ First-degree relative with diabetes

▪ High-risk race/ethnic group

▪ Women who delivered a baby > 9 pounds or were diagnosed with gestational
diabetes (GDM)
 Risk Factors
▪ High-density lipoprotein cholesterol (HDL-C) <35 mg/dL ± triglyceride (TG) >250
mg/dL

▪ Hypertension

▪ Conditions associated with insulin resistance (eg, severe obesity, acanthosis

nigricans, polycystic ovarian syndrome), Cardiovascular disease (CVD) history.
 Metabolic Syndrome ?
▪ A cluster of common abnormalities, including insulin resistance, impaired
glucose tolerance, abdominal obesity, reduced high-density lipoprotein (HDL)-
cholesterol levels, elevated triglycerides, and hypertension.
▪ Increases risk of cardiovascular disease and diabetes
▪ Obesity, an atherogenic diet, and physical inactivity are the strongest risk
factors for the development of metabolic syndrome.
▪ Lifestyle interventions, including a diet low in saturated fats and moderate to
intense physical activity, are the mainstay of treatment.
 Prediabetes
▪ Prediabetes is a condition in which the blood sugar level is higher than
normal, but not high enough to be classified as diabetes.

▪ Important ?!
 INVESTIGATIONS
▪ One of four tests can be used to establish a firm diagnosis of diabetes:
▪ Fasting plasma glucose.
▪ Random plasma glucose ≥200 mg/dL with diabetes symptoms.
▪ 2-hour post-load glucose.
▪ HbA1C.

▪ All of these require confirmation with a second test, which may be the same test or a
different test. This means a single blood sample is sufficient to establish a diabetes diagnosis if
assays of both HbA1c and fasting plasma glucose meet criteria for diabetes diagnosis.
 Fasting Plasma Glucose
▪ Normally, FPG should be less than 100 mg/dL.
▪ Values between [100 mg/dL – 125 mg/dL] Represents Impaired FPG levels or
Prediabetes.
▪ Fasting plasma glucose >6.9 mmol/L (>125 mg/dL) Represents Diabetes.
 Post-Prandial Glucose Tolerance Test
▪ Normally, OGTT should be less than 140 mg/dL.
▪ Values between [140 mg/dL – 199 mg/dL] Represents Impaired OGTT levels
or Prediabetes.
▪ Values above or equals 200 mg/dL, Represents Diabetes.
 Glycated hemoglobin [HbA1c]
▪ Glycated hemoglobin [HbA1c] is a form of hemoglobin (Hb) that is chemically linked to a
sugar.
▪ Normal values are less than 5.7 %
▪ Values between 5.7 – 6.4 % Represents Prediabetes.
▪ Values ≥ 6.5 Represents Diabetes.
To Summarize
Blood
Glucose HbA1c FPG PPPG
Parameter
< 5.7%
Normal < 100 mg/dl < 140 mg/dl

100-125 mg/dl 140-199 mg/dl

Pre-diabetes 5.7 - 6.5
(IFG) (IGT)

126 mg/dl or 200 mg/dl or

Diabetes ≥ 6.5%
above above
If you reach a diagnosis of DM
▪ Blood pressure, smoking status, fasting lipid levels, urine albumin/creatinine ratio,
serum creatinine with eGFR.

▪ Clinical assessment of cardiac, carotid, and peripheral circulation, with ECG and vascular
investigation (e.g.,Screen for peripheral arterial disease using an ankle-brachial index)
can be considered if age of the patient >50

▪ Examination of the feet, including assessment of ankle reflexes, pulses, vibratory

sensation, and monofilament touch sensation.

▪ Dilated retinal examination should be part of the evaluation.

 There are various tests available for
measuring albuminuria; however, the
recommended method is to measure UACR
Measurement of albuminuria 1

Albuminuria test Normal Microalbuminuria Macroalbuminuria Advantages Disadvantages

Dependent on level of
Dipstick for protein – – + Convenience
hydration

24-hour protein Overcomes problem of Subject to collection

<150 <500 ≥500
(UPCR or mg/24 hours) diurnal variation in excretion errors

24-hour albumin Overcomes problem of Subject to collection

<30 30–300 >300
(UACR or mg/24 hours) diurnal variation in excretion errors

Timed collection (μg/ Overcomes problem of Subject to collection

<20 20–200 >200
min) diurnal variation in excretion errors

Convenience – not
Spot collection
<30 30–300 >300 dependent on hydration level Ratios vary based on sex
(UACR)
Most reproducible

UACR, urine albumin:creatinine ratio; UPCR, urinary protein:creatinine ratio

1. Basi S, et al. Diabetes Care 2008;31:S194–201; 2. The Renal Association. The UK eCKD Guide: Proteinuria. Available at: https://renal.org/information-resources/the-uk-eckd-guide/proteinuria/
(Accessed February 2020)
 COMPLICATIONS
▪ Although the etiologies of type 1 and type 2 diabetes differ dramatically, both
lead to hyperglycemic states, and both share common macrovascular and
microvascular complications.
COMPLICATIONS
COMPLICATIONS
 Macrovascular Complications
▪ Coronary artery disease and stroke are the most common manifestations, and account for most
deaths in people with diabetes. Modification of cardiovascular risk factors (e.g., hypertension,
dyslipidemia) are important long-term treatment issues.

▪ Peripheral arterial disease (PAD) includes a range of arterial syndromes that are caused by
atherosclerotic obstruction of the lower-extremity arteries.

▪ Stroke is defined as an acute neurological deficit lasting more than 24 hours and caused by
cerebrovascular etiology.
Diabetic Retinopathy
Is the retinal consequence of chronic progressive diabetic microvascular leakage and occlusion.
Types:
◦ Non-proliferative:NPDR
◦ nonproliferative Staging
◦ Mild NPDR : -MAs only(microaneurysm)
◦ Moderate NPDR : venous beading, intraretinal microvascular aneurysms, intraretinal haemorrhage, and
Cotton wool spots hard exudates.
◦ SeverNPDR:>20 intraretinal haemorhage,venous beading in tow or more quadrants
◦ Proliferative PDR: Neovascularization.
Diabetic Retinopathy
The AAO recommends screening for retinopathy as follows:
◦ In type 1 diabetes: 5 years after onset, with yearly follow-up.
◦ In type 2 diabetes: at time of diagnosis, with yearly follow-up.

Management
◦ Control of hyperglycemia, BP and other factors. [ Will reduce progression ]
◦ Non-severe NPDR in the absence of clinically significant macular edema requires observation only.
◦ Non-severe NPDR with clinically significant macular edema requires intravitreal (VEGF) therapy.
◦ PDR at high-risk should be treated with pan-retinal photocoagulation.
 Diabetic Nephropathy
▪ It starts with glomerular hyper-filtration, proceeding to microalbuminuria, gross proteinuria,
nephrotic syndrome and CRF.

▪ Defined by albuminuria (urinary albumin 30 mg/g- 300 mg/g ), and is typically associated with
retinopathy.
Diabetic Nephropathy
Populations to screen for DKD:
◦ Type 1 diabetic patients - 5 years after diagnosis.
◦ Type 2 diabetic patients - at the time of diagnosis.

Management:
◦ Control of hyperglycemia
◦ First-line treatment should include ACE inhibitors ARBs. ACE inhibitors slow progression of DKD in type
1 and type 2 diabetic patients with moderately increased albuminuria.
◦ 2nd line therapy Non-dihydropyridine CCB.
◦ Treatment of dyslipidemia
◦ Smoking Cessation
 Renal and cardiovascular disease are
interconnected and should be considered
together Renal and cardiac systems are linked1 CKD patients are more likely to die of heart
disease than advance to ESRD2

ESRD CV
death

Therefore renal and cardiac systems and outcomes should be considered together
CKD, chronic kidney disease; CV, cardiovascular; ESRD, end-stage renal disease.
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1. Ronco C, et al. J Am Coll Cardiol. 2008;52:1527. 2. Dalrymple L, et al. J Gen Intern Med. 2011;26:379.
 Diabetic Neuropathy
▪ Is a highly prevalent complication of diabetes and is characterized by the presence of symptoms
and/or signs of peripheral nerve dysfunction and/or autonomic nerve dysfunction.

▪ The most common symptoms are induced by the involvement of small fibres and include: Pain,
Dysaesthesias (abnormal sensations of burning, tingling, numbness).
▪ Pain is often worse at night and may disturb sleep.
Diabetic Neuropathy
Classification for diabetic neuropathy
◦ Diffuse neuropathy
◦ Distal symmetrical sensorimotor polyneuropathy
◦ Autonomic neuropathy
◦ Mononeuropathy
◦ Isolated cranial or peripheral nerve (e.g., CN III, ulnar, median, femoral, peroneal)
◦ Mononeuritis multiplex (multifocal neuropathy)
◦ Radiculopathy or polyradiculopathy
◦ Radiculoplexus neuropathy (also called lumbosacral polyradiculopathy or proximal motor amyotrophy)
◦ Thoracic radiculopathy
Diabetic Neuropathy
Autonomic neuropathy
◦ Exercise intolerance due to a reduced response in heart rate and blood pressure (BP)
◦ Orthostatic hypotension, GI autonomic neuropathy, Esophageal dysfunction, Intermittent diarrhea,
Erectile dysfunction (ED) is present in 30% to 75% of diabetic men.
◦ Bladder dysfunction and impaired ability to void is present in up to 50% of people with diabetes
Diabetic Neuropathy
◦ The most common forms are chronic sensorimotor
polyneuropathy and autonomic neuropathy.

◦ There are no distinguishing features unique to DN,

so all other possible causes of the neuropathy
(e.g., hypothyroidism, vitamin B12 deficiency, uraemia,
chronic alcoholism) must be ruled out by careful history,
physical examination, and laboratory tests.
 Diabetic Neuropathy Management
▪ Glycemic control.
▪ Proper care of the foot.(OFF LOUDING IN CASE OF ULCER)
▪ Pain management:
▪ By ADA, Pregabalin, duloxetine, and gabapentin are considered first-line pharmacotherapies.
Diabetic Foot
◦ The term 'diabetic foot complications' encompasses the conditions of diabetic foot ulcer, and diabetic
foot infections.
◦ Foot examination should include inspection of the skin, assessment of foot deformities, neurologic
assessment (10-g monofilament testing with at least one other assessment: pinprick, temperature,
vibration), and vascular assessment including pulses in the legs and feet.
Diabetic Foot
◦ Patients with symptoms of claudication or decreased or absent pedal pulses should be referred for ABI
and for further vascular assessment as appropriate.
◦ Provide general preventive foot self-care education to all patients with diabetes.
◦ The use of specialized therapeutic footwear is recommended for high-risk patients with diabetes
including those with severe neuropathy, foot deformities, or history of amputation.
Management of Diabetes
 MANAGEMENT
Prevention should be the main focus of care;
Identify individual at risk for diabetes such as prediabetes or history of gestational diabetes
Support lifestyle intervention by weight loss7% with 150 min/week of exercise to prevent
progression to T2DM in individual at risk
For every kilogram of weight loss risk was reduced by 16% (ADA.SOC)
Physical activity independent of weight loss was formed to reduce development ofT2DM by 44%
The paradigm of diabetes management has shifted over the past decade from a predominantly
glucose-centric approach to approaches that prioritise prevention of diabetes complications
Management of diabetes require reducing glucose levels to a safe patient centred rang using
glucose lowering drugs base for reduction of diabetes complications and excess adiposity, not
just lowering level of HbA1c
 Lifestyle Modifications
▪ Nutrition therapy involves limiting caloric intake to achieve recommended weight, while offering
a diversified and appealing menu of food choices. Preferably by a nutritionist.
▪ Moderate physical activity is recommended as tolerated.
▪ Adults should engage in 3 to 4 sessions of aerobic physical activity per week, with each session lasting
on average 40 minutes.
▪ In addition, gentle strength training that targets all major muscle groups may be beneficial if done for
20 minutes 2 to 3 times per week on non-consecutive days.
▪ People should be encouraged to limit the amount of time they spend being sedentary.
 Lifestyle Modifications
▪ Smoking cessation
▪ Blood Pressure Control
▪ The ADA recommends management of lipid abnormalities.
▪ An assessment of sleep duration and quality should be considered.
▪ HbA1c goals should be individualized.
▪ For many patients, the goal HbA1c <7% is appropriate. However, HbA1c 7.0% to 7.9% may be
more appropriate in some patients, such as those with advanced age, limited life expectancy,
known cardiovascular disease, high risk of severe hypoglycemia, or difficulty achieving lower
HbA1c goals despite use of multiple antihyperglycemic medications and insulin.
Glycemic Monitoring and Targets in Patients with
Diabetes and CKD
Recommendation 2.2.1. We recommend an individualized HbA1c target
ranging from <6.5% to <8.0% in patients with diabetes and CKD not treated
with dialysis (Figure 9) (1C).
▪ TheADA SOC recommend starting treatment immediately at the time of T2DM diagnosis
▪ Early treatment and achieving an A1c <7% is associated with decreased microvascular
complication
▪ Choice of agents should be individualized, taking into account patient values and preferences,
the likelihood that an agent reduces all-cause or cardiovascular mortality, renal effects, adverse
effects, costs, and other factors.
Glycemic Recommendations :
▪ A1C <7.0%,
▪ Preprandial capillary plasma glucose 80–130 mg/dL
▪ Peak postprandial capillary plasma glucose less than 180mg/dl
▪ Among the antihyperglycemic medications that reduce cardiovascular mortality in some patient
subgroups are metformin, empagliflozin, canagliflozin, and liraglutide.
Pharmacological treatment
Metformin
First-line treatment in type 2 diabetes.
Can promote weight loss and may reduce cardiovascular events and mortality. Low risk for
Hypoglycemia.
Pharmacology
◦ Metformin reduces liver (hepatic) production of glucose, decreases the intestinal absorption of glucose,
and enhances insulin sensitivity by increasing both peripheral glucose uptake and utilization.
◦ Daily optimal dose are 1.5g to 2.5g.
◦ Effects on HbA1C: 1-2%
Metformin
Side effects
◦ GI Upset.
◦ Lactic acidosis.
◦ Contraindicated if eGFR < 30
◦ Vitamin B12 deficiency.
◦ Current guidelines from the ADA/Erupean association for
◦ The study of diabetes and the American association of clinical
Endocrinology no longer recommend metformin as the
Preferred first line agent for all patient with T2DM
◦ THEY SUGGEST consideration of cardiac and kidney
comorbidities when selecting first line treatment
Metformin and Renal impairment

https://www.medicines.org.uk/emc/medicine/23244/SPC, last updated 12 Feb. 2018

Sodium-glucose cotransporter 2
inhibitors SGLT2-Inhibitors
Effects on HbA1C: 1%
Examples: Canagliflozin, dapagliflozin, empagliflozin
There is evidence that use of SGLT2 inhibitors prevents major kidney outcomes. Empagliflozin
and canagliflozin have been shown to reduce cardiovascular risk.
Pharmacology
◦ Block reabsorption of glucose in proximal convoluted tubule.

Side effects
◦ Glucosuria (UTIs, vulvovaginal candidiasis), dehydration (orthostatic hypotension), weight loss.
◦ Use with caution in renal insufficiency .
◦ Risk of euglycemic diabetic ketoacidosis when used with ketogenic low carbohydrate diet
GLP-1 analogs
Examples: Exenatide, liraglutide, Semaglutide
Effects on HbA1C: up to 1.5%
Pharmacology:
◦ Decrease glucagon release,delay gastric emptying. Increase glucose-dependent insulin release.
◦ may reduce cardiovascular events and mortality. Low risk of hypoglycemia.
◦ High dual efficacy in lowering glucose and promoting weight loss

Side effects:
◦ Nausea, vomiting. Weight loss, decrease satiety.
◦ Pancreatitis
◦ Contraindicated in Medullary thyroid cancer
Many of newer antidiabetis medication such as GLP-1 receptor agonists and SGLT2 inhibitors
Target glucose control and lower cardiorenal risks DUAL TARGETED APPROACH
-Patient with CVD or who have risk factor for CVD(>55year old,with two or more risk factor:HTN,
aAlbuminuria,Obesity,dislipidemia,Smoking. Shuold be treated with either GLP-1 or SGLT2 or
both for patient with persistant elevated A1c.
SGLT2 may be used for patient with GFR >20ml/min and for patient with stag 3 CKD
Approaches to Management of Patients with Diabetes
and CKD
Practice Point 5.2.1: Team-based integrated care, supported by decision-makers, should
be delivered by physicians and nonphysician personnel (e.g., trained nurses and
dieticians, pharmacists, health care assistants, community workers, peer supporters)
preferably with knowledge of CKD (Figure 33).
65
Figure 27. Dosing for available GLP-1 RA agents and dose modification for CKD
 2020 KDIGO Treatment Algorithm for
Patients with T2D and CKD
Lifestyle therapy
Physical activity
Nutrition
Weight loss

Metformin SGLT-2i
First-line therapy
eGFR <45: reduce dose eGFR <30: do not initiate
eGFR ≥30 mL/min/1.73m2
eGFR <30 or dialysis: DC Dialysis: DC

GLP-1 RA
Additional drug (preferred)
• Guided by patient preferences, comorbidities,
therapy as needed DPP-4i Insulin eGFR and cost
for glycemic control • Includes patients with eGFR<30 mL/min/1.73m2
SU TZD or treated with dialysis
AG-i
AG-i = alpha-glucosidase inhibitor; CKD = chronic kidney disease; D/C = discontinue; DPP-4i = dipeptidyl peptidase-4 inhibitor; eGFR = estimated glomerular filtration rate; GLP-1 RA = glucagon-like
peptide-1 receptor agonist; SGLT2-i = sodium-glucose cotransporter 2 inhibitor; SU = sulfonylurea; T2D = type 2 diabetes; TZD = thiazolidinedione.
67
de Boer IH et al. Kidney Int. 2020;98:839-848.
 Guidelines recommend specific therapies
to reduce kidney and cardiovascular risks in
patients
ADAwith
2020 CKD andESC/EASD
T2D 2019 KDIGO 2020*
1 2 3

Recommended for treatment

ACEi Strongly recommended in patients with
of hypertension, particularly Recommended in patients with
hypertension and UACR ≥300 mg/g
/ and/or eGFR <60ml/min/1.73 m2 in presence of UACR ≥30 mg/ diabetes, hypertension and
ARB g, proteinuria or left ventricular albuminuria
Recommended in patients with
s hypertension and UACR 30–299 mg/g hypertrophy

Consider in patients with an eGFR Recommended if

eGFR is Recommended in combination
SGLT ≥30 ml/min/1.73 m 2 and UACR >30 mg/ with metformin in patients with
g, particularly those with UACR >300 30–<90 ml/min/1.73 m2
-2i T2D, CKD and an eGFR ≥30
mg/g, to reduce risk of CKD progression, (associated with lower risk of ml/min/1.73 m2
CV events, or both renal endpoints)
Suggested if A long-acting GLP-1RA is
May reduce risk of progression of recommended in patients with
GLP- albuminuria, CV events, or both in
eGFR >30 ml/min/1.73 m2
T2D and CKD who have not
1RA (liraglutide and semaglutide
patients with CKD and increased achieved individual
CV risk associated with lower risk of glycaemic targets despite
renal endpoints) use of metformin/SGLT-2i
*The KDIGO 2019 Clinical Practice Guideline on Diabetes Management in Chronic Kidney Disease is currently available for public review
ACEi; angiotensin-converting enzyme inhibitor; CKD, chronic kidney disease; CV, cardiovascular; eGFR, estimated glomerular filtration rate; GLP-1RA, glucagon-like peptide-1 receptor
agonist; SGLT-2i, sodium-glucose co-transporter-2 inhibitor; T2D, type 2 diabetes; UACR, urinary albumin-to-creatinine ratio
1. ADA. Diabetes Care 2020;43:S135–S151; 2. Cosentino F, et al. Eur Heart J 2019;40:3215–3217; 3. KDIGO. Clinical practice guideline on diabetes management in chronic kidney disease.
Public review draft; December 2019. https://kdigo.org/wp-content/uploads/2018/03/KDIGO-Diabetes-Management-in-CKD_Public-Review.pdf [accessed August 2020]
68
Thiazolidinediones
Effects on HbA1C: 1%
Pharmacology
◦ Decrease hepatic gluconeogenesis, Improves response to insulin

Side effects
◦ Weight gain, edema, HF, risk of fractures.
◦ Increase risk of MI, cardiovascular death.
◦ Contraindicated in HF, Hepatic impairment.
◦ Pioglitazone(Actos) has been shown to increase the risk of bladder cancer
DPP-4 inhibitors
Examples: Linagliptin, saxagliptin, sitagliptin
Effects on HbA1C: 0.8%
Suitable for obese patients without gastroparesis who desire weight loss. Low risk of
hypoglycemia.
Has beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2
diabetes.
Pharmacology:
◦ Inhibit DPP-4 enzyme that deactivates GLP-1, decrease glucagon release, gastric emptying. Increase
glucose-dependent insulin release.
Side effects:
◦ Respiratory and urinary infections, weight neutral.
◦ Decrease satiety (often desired).
Sulfonylurea
Examples: Sulfonylureas (1st gen)Chlorpropamide, tolbutamide Sulfonylureas (2nd gen)
Glipizide, glyburide.
Effects on HbA1C: 1-2%
May reduce microvascular complications, but confer no mortality benefit.
Pharmacology:
◦ Close K+ channels in pancreatic B cell membrane, cell depolarizes, increased insulin release via Ca2+
influx.

Side effects: Hypoglycemia, weight gain.

α-Glucosidase inhibitors.
• Acarbose (Precose), Miglitol (Glyset).

❑ Mechanism of action:
• Inhibit break down of disaccharides.
• Delay carbohydrate absorption in brush border of small intestine.
• Flattening the postprandial glycemic curve.
❑ Advantages:
• No hypoglycemia
α-Glucosidase inhibitors.
Side effects and precaution:
• Flatulence, abdominal pain .
• Contraindicated with GI disorders
• Contraindicated with cirrhosis.
Insulin Therapy
CONSIDER INSULIN THERAPY AT ANY AGE IN PATIENT WHO NEED IT BUT
ADJUST DOSES OF OTHER GLUCOSE LOWERNG MEDICATION TO PREVENT
HYPOGLYCEMIA