Highlights. Dr Mick Kumwenda MSc FRCP (London) Consultant Nephrologist and Clinical Director (Medicine) Glan Clwyd Hospital Rhyl Denbighshire UK Mick.firstname.lastname@example.org. PACD18 2014.
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Dr Mick Kumwenda MSc FRCP (London)
Consultant Nephrologist and Clinical Director (Medicine)
Glan Clwyd Hospital
We are delighted to present you with the highlights this year from yet again a very successful congress attended by 2003 multidisciplinary delegates from around the globe.
We wish to thank all those who attended and hope you left the congress full of knowledge that made a difference when you returned back to your home base.
We also thank all the speakers that contributed, the quality of all the papers was exceptional and we have selected a few slides with the kind permission of the presenters to summarise key messages from the congress.
The PACD continues to serve the diabetes health care providers in the Middle East as an academic forum for the exchange of knowledge, training and experience.
Conference chair : Sherif Hafez
Vice chairs: Mohamed Fahmy Abdel-Aziz
Megahed Abou El-Magd
Assistant Secretary General: Gamela Nasr
Hyam Refaat Tantawi
Type 2 diabetes (T2D) is a complex disorder
that is affected by multiple genetic and environmental factors.
Existing genetic markers explain only a
modest (15%) part of the heritability of T2D.
Epigenetics has been defined as heritable changes in gene function that occur without a change in the nucleotide sequence.
Non -sequence dependent inheritance
(Schwartz, M.W. et al., 2013)
DiabetesDual defect of type 2 diabetes: treating a moving target
Diagnosis oftype 2 diabetes
Progression oftype 2 diabetes
IGT ± Obesity
DeFronzo et al. Diabetes Care 1992;15:318-68
Patients are responsible
Patients are therefore the final decision-makers
Knowing what is best for diabetes, is not the same as knowing what is best for that patient
These principles have re-defined how we provide education
Both structured education and one to one approach benefits patients.
TRIPOD=Troglitazone in Prevention of Diabetes Study; PIPOD= Pioglitazone in Prevention of Diabetes Study;
STOP-NIDDM=Study to Prevent Non–Insulin-Dependent Diabetes Mellitus; NAVIGATOR=Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research; DREAM=Diabetes Reduction Approaches with Ramipril and Rosiglitazone; XENDOS=Xenical in the Prevention of Diabetes in Obese Subjects; ORIGIN=Outcomes Reduction with Initial Glargine Introduction.
ADA. V. Diabetes Care. Diabetes Care 2014;37(suppl 1):S27. Figure 2;adapted with permission from Inzucchi SE, et al. Diabetes Care 2012;35:1364–1369
The A1C and ABCDE of glycaemia management in type 2 diabetes: a physician's personalized approach.
Pozzilli P, Leslie RD, Chan J, De Fronzo R, Monnier L, Raz I, Del Prato S.
The A1C and ABCD of glycaemia management in type 2 diabetes: a physician's personalized approach.Diabetes Metab Res Rev. 2010 May;26(4):239-44.
Baseline HbA1c (%)
Diabetes duration (years)
Glycated Hb reduction vs insulin alone
Yki Jarvinen H Diabetes Care 2001 24 : 738-67
COUNTER REGULATORY HORMONES: GLUCAGON, EPINEPHRINE, CORTISOL, GROWTH HORMONE
All refs Diabetes Metab (2003): 1Gianarelli R vol. 29:6S28-35; 2Després JP 29:6S53-61;
3Grant PJ ;29:6S44-52; 4Wiernsperger N 29:6S77-8; 5Schäfers RF 29:6S62-70;6Beisswenger 29:6S95-103; 7Leverve XM 29:6S88-94; 8Mamputu JC 29:6S71-6;
Balakumar P, et al. Cell Signal. 2013 Sep;25(9):1799-803
Metformin was well tolerated, albeit with a trend towards increased hypoglycaemia. Formal estimates of combined effects from the five trials which reported appropriate data indicated a significant reduction in insulin dose (6.6 U/day, p<0.001) but no significant reduction in HbA1c (absolute reduction 0.11%, p=0.42). No reported trials included cardiovascular outcomes
Raju B, et al. J Clin Endocrinol Metab. 2006 Jun;91(6):2087-92.
Riccardi G, et al. Diabet Med. 1999 Mar;16(3):228-32.
Strowig SM, Raskin P. Diabetes Care. 2005 Jul;28(7):1562-7.
Shimada A, et al. Diabetes Metab Res Rev. 2011 Nov;27(8):951
Yang Z, et al. Diabetes Res Clin Pract. 2009 Jan;83(1):54-60.
Hari Kumar KV, Shaikh A, Prusty P. Diabetes Res Clin Pract. 2013 May;100(2):e55-8
Oral hypoglycemic agents
Unsuitable for use during fasting because of the inherent risk of
Hypoglycemia, use with caution. Consider dose adjustment.
No treatment adjustment required 2–4 weeks to exert substantial antihyperglycemic effects
The best tolerated drugs, Consider DPP4i as an alternative to SUs if the risk of hypoglycemia is high
Modify timing of doses: Two thirds of dose at Iftar
• One third at suhur.
Take twice daily at suhur and iftar
E Hui et al , BMJ, 26 june 2010 , Volume 340; Al-Arouj M. et al, Recommendations for management of diabetes during Ramadan. Diabetes Care. 2010;33: 1895-1902.
No Diabetes/CVD (n=3,503)
Diabetes/No CVD (n=569)
No Diabetes/No CVD (n=2,796)
OASIS=Organization to Assess Strategies for Ischemic Syndromes
Malmberg K, et al. Circulation. 2000;102:1014-1019.
> 2.5 mg/mmol males
> 3.5 mg/mmol females
30 - 300mg/day
> 25 mg/mmol both males and females
> 300mg/day – diabetic nephropathy
(low serum albumin = nephrotic syndrome
Class 1 – EM proven GBM thickening
Class 2a – Mild mesangial expansion
Class 2b – Severe mesangial expansion
Class 3 - Nodular sclerosis ( KW lesions)
Class 4 - Advanced sclerosis ( > 50% glomeruli)
Tervaert TC et al J Am Soc Nephrol 2010 online
Persistent albuminuria categories
Description and range
Prognosis of CKD by GFR
and Albuminuria Categories:
GFR categories (ml/min/ 1.73 m²)
Description and range
Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk; Orange: high risk; Red, very high risk.
KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3:136-150. http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf Accessed February 26, 2013
Although we understand the natural history of diabetic kidney disease some patients with type 2 diabetes progress to end stage kidney disease without developing proteinuria
Conclusion: patients with type 2 diabetes can commonly progress to a significant degree of renal impairment while remaining normoalbuminuric.
MacIsaac et al, Diabetes Care. 2004 Jan;27(1):195-200
1: Canadian Hypertension Education Program (CHEP) 2014 Recommendation, adopted from: https://www.hypertension.ca/chep. Accessed at 5/2/2014
2: Mancia G, et al. J Hypertens. 2013 Jul;31(7):1281-357
3: James PA, et al. JAMA. 2013 Dec 18. [Epub ahead of print]
BP & Lipid targets
Aspirin, Statin, ACEI
CV morbidity & mortality -50%
Compared to usual diabetic care
8 years follow up
Progression to proteinuria -60%
Progression to Retinopathy -60%
Gaede P et al. Multifactorial intervention , N Engl J Med 2003; 348: 383 -93
Number of microalbuminuric patients with type 2 diabetes needed to treat for 13 years to prevent one …..
Death 5 patients
Cardiovascular death 8 patients
Major cardiovascular event 3 patients
Progression to nephropathy 5 patients
Dialysis 16 patients
Laser treatment 7 patients
Steno-2 Trial: multiple risk factor intervention in T2DM
- nephrotic syndrome
- e GFR < 40ml/min
-Bone mineral disease
- phosphorus 800-1000mg/day
- salt intake <6g/day
- anaemia Hb 10-12g/dl
- ferritin >100ng/ml
Microalbuminuria remains the gold standard
Other candidate markers associated with microalbuminuria or low e GFR:
- Neutrophil gelatinase associated lipocalin (NGAL)
- Kidney Injury Molecule 1(KIM 1),
-Transforming Growth Factor Beta
-Tumour Necrosis Factor
Adipocytokinine Zinc alpha 2 glyco protein (ZAG) in non-albuminurics
Efficacy of Antiplatelet Therapies in ACSResults in the Diabetes Mellitus Subgroups (Adapted from Ferreiro JL et al. Circulation 2011; 123: 798-813)
Piccini JP et al,Am J Med 2004: 116: 64s-75s
Trost S, LeWinter M. Curr Treat Options Cardiovasc med. 2001: 3: 481-492
PDE-5 inhibitors improve relaxation of smooth muscle. Contraindicated in patients receiving nitrates, recent stroke/MI, unstable angina