Complications of diabetes mellitus

I Acute 1. Metabolic and Subacute 2. Infections Ketoacidosis coma Hyperosmolar non-ketotic coma Lactic acidosis Hypoglycaemia Bacterial, fungal !kin, mucosa, soft tissues, urinary tract, lungs, bone

II. Chronic 1. Macroangiopat"y #oronary "eart disease, cerebro$ascular disorders, perip"eral $ascular disease 2. Microangiopat"y %etinopat"y, nep"ropat"y, dermopat"y, &europat"y '. Miscellaneous (iabetic foot, cardiomyopat"y, ocular complications ot"er t"an retinopat"y, erectile impotence.

ACUTE COMPLICATIONS O !M )cute complications of (M include "# (iabetic ketoacidosis *(K)+ $# &on ketotic "yperosmolar coma *&KH#+ %# Hypoglycemia. &# Lactic acidosis !IA'ETIC (ETOACI!OSIS )!(A# (K) is medical emergency and mortality is about ,-1- .. #ardinal features are "# Hyperglycemia $# Hyperketonemia %# Metabolic ketoacidosis Pathoph*siolo+* (K) results from relati$e or absolute insulin deficiency combined /it" counter regulatory "ormone e0cess *glucagon, catec"olamines, cortisol, and gro/t" "ormone+. 1"e decreased ratio of insulin to glucagon promotes gluconeogenesis, glycogenolysis, and ketone body formation in t"e li$er, as /ell as increases in substrate deli$ery from fat and muscle *free fatty acids, amino acids+ to t"e li$er. Ketosis results from a marked increase in free fatty acid release from adipocytes, /it" a resulting s"ift to/ard ketone body synt"esis in t"e li$er. Ketones produced are beta "ydro0y butyric acid, acetone and acetoacetate.

 Clinical features, S*mptoms &ausea3$omiting Ph*sical findin+s 1ac"ycardia

1"irst3polyuria )bdominal pain !"ortness of breat"

(e"ydration and "ypotension 1ac"ypnea3Kussmaul respirations )bdominal tenderness *may resemble

acute pancreatitis or surgical abdomen+ 6btundation

#oma
Precipitatin+ e-ents Inade2uate insulin administration

Infection *pneumonia341I3gastroenteritis3sepsis+ Infarction *cerebral, coronary, mesenteric, perip"eral+ (rugs *cocaine+ 5regnancy
!ifferential dia+nosis !imple "yperglycemia Hyperglycemic hyperosmolar state !tar$ation ketosis )lco"olic ketoacidosis

Laborator* Abnormalities (K) is c"aracteri7ed by "yperglycemia, ketosis, and metabolic acidosis *increased anion gap+ 4rine )cetoacetate is detected by used ketosis detection reagent *nitroprusside+ !erum potassium at presentation may be mildly ele$ated. 8le$ated blood urea nitrogen *B4&+ and serum creatinine le$els reflect intra$ascular $olume depletion Leukocytosis, "ypertriglyceridemia, and Hyperamylasemia*sali$ary origin +are commonly found as /ell.

Mana+ement of !iabetic (etoacidosis

#onfirm diagnosis *9 plasma glucose, positi$e serum ketones, metabolic acidosis+. )dmit to "ospital: intensi$e-care setting may be necessary for fre2uent monitoring or if pH ; <.-- or unconscious. )ssess !erum electrolytes, )cid-base status, urine ketones, renal function a# luid replacement. luid - -.=. saline *&a#l+ i.$.

/ate - 1 liter o$er '- minutes follo/ed by 1 liter o$er 1 "r, 1 liter o$er 2 "rs, 1 liter
o$er ne0t 2-> "rs ?"en blood glucose ; 2<- mg3dl !/itc" to ,. de0trose, 1 litre @-"ourly

1ypical re2uirement is A litres in first 2> "rs but a$oid fluid o$erload in elderly
patients !ubse2uent fluid re2uirement s"ould be based on clinical response including urine output b# Insulin ,- unitBs soluble *plain+ insulin in ,- ml -.=. saline i.$. $ia infusion pump A units3"r initially follo/ed by ' units3"r #"eck blood glucose "ourly initially-if no reduction in first "our, rate of insulin infusion s"ould be increased )im for fall in blood glucose of ,,-11- mg3dl per "our c# Serum potassium If plasma potassium ; '., mmol3l, gi$e >- mmol of K#L per 1 litre of fluid

If plasma potassium is '.,-,.- mmol3l, gi$e 2- mmol of K#L per 1 litre of fluid If plasma potassium is C ,.- mmol3l, gi$e no added potassium

ADDITIONAL PROCEDURES IN THE MANAGEMENT OF DIABETIC KETOACIDOSIS #at"eterisation if no urine passed after ' "rs &asogastric tube to keep stomac" empty in unconscious or semiconscious

patients, or if $omiting is protracted #entral $enous line if cardio$ascular system compromised, to allo/ fluid replacement to be adDusted accurately 5lasma e0pander if systolic B5 is ; =- mmHg or does not rise /it" i.$. saline

)ntibiotic if infection demonstrated or suspected 8#E monitoring in se$ere cases #ontinue abo$e until patient is stable, glucose goal is 1,-F2,- mg3dL, and acidosis is resol$ed. Insulin infusion may be decreased to -.-,F-.1 units3kg per "our. )dminister intermediate or long-acting insulin as soon as patient is eating. )llo/ for o$erlap in insulin infusion and subcutaneous insulin inDection.
Cerebral oedema- Treat with mannitol, oxygen Acute respiratory distress syndrome Thromboembolism Disseminated intravascular coagulation (rare) Acute circulatory ailure

Complications

Non 0etotic 1*perosmolar coma )N(1C# &KH# is c"aracteri7ed by se$ere "yperglycemia and /it" or /it"out significant ketoacidosis. More common in elderly and mortality is about ,--@-.. Garious differences bet/een (K) and &KH# are gi$en t"e bo0.
!lasma glucose (mg"dl) !lasma )etones DKA #$%-&$% **** (+$-'%% mg"dl $-+% mmol"l) -ow. 2levated, normal, may be low 5 '% 0 '+ 5 67# 5 ##% * *** HONC &%%-'(%% *

,erum sodium !otassium 4icarbonate (m23"l) Anion gap (m23"l) 4lood pH 9smolality (m9sm"l) /aised blood urea nitrogen Haematocrit (dehydration)

/aised (0'1% m23"') /aised"normal 0 '& '%-'+ 8ormal #1%-#$% ** ****

"# Serum osmolalit* 2 2*&a HK+ Hurea3,.A Hglucose31@.normal serum osmolality is 2@-'-- mosmols3kg $# Anion +ap F *&a H K+ F *#l H H#6'+. &ormal anion gap is 1--12. )E is markedly increased in (K) but normal to "ig" in &KH#. Mana+ement. Management of &KH# is same as (K) /it" some differences "# &KH# is $ery sensiti$e to insulin so "alf t"e dose of insulin is used.

$# !"ould use .>,. of &a#l until serum osmolality is normal t"en normal *.=.+ saline can be used. I Hypoglycemia is discussed in detail later. I Lactic acidosis in diabetic patients can be caused due to infection or metformin.

C1/ONIC COMPLICATIONS O !M
Patho+enesis Jour t"eories "a$e been proposed to e0plain "o/ "yperglycemia mig"t lead to t"e
c"ronic complications of (M 1+ Jormation of ad$anced glycosylation end products *)E8s+ $ia t"e nonen7ymatic glycosylaton of intra- and e0tracellular proteins. 2+ Increase glucose metabolism $ia t"e sorbitol pat"/ay '+ Jormation of diacylglycerol leading to acti$ation of protein kinase # *5K#+ >+ "yperglycemia increases t"e flu0 t"roug" t"e "e0osamine pat"/ay, /"ic" generates fructose-A-p"osp"ate.1"is alters t"e function by glycosylation of proteins. )ny of t"e abo$e one or more t"erioes lead to altered cell functions, renal and $ascular connnceti$e tissue c"anges etc finally leading to $acular damage t"us resulting in c"ronic complications of diabetes.

1"e (iabetes #ontrol and #omplications 1rial *(##1+,

1"e 4nited Kingdom 5rospecti$e (iabetes !tudy *4K5(!+ and Kumamoto study pro$e t"e $alue of metabolic control and emp"asi7e t"e importance of *1+ intensi$e glycemic control in all forms of (M, and *2+ early diagnosis and strict blood pressure control in type 2 (M.

(iabetic nep"ropat"y is t"e most important cause of 8!%( all o$er t"e disease. Garious stages of diabetic nep"ropat"y are "# !tage of "yperfiltration $# !tage of microalbuminuria *'--'--micrograms of albumin3day+ %# !tage of o$ert proteinuria. (uring t"is stage patient may "a$e nep"rotic range of proteinuria. &# 8nd stage renal disease*8!%(+ 5attern of progression of diabetic nep"ropat"y

!iabetic nephropath*

 5at"ological c"anges include t"icking of glomelular basement membrane and later nodular deposits /it" glumeruloscerosis *Kimmelsteil-/ilson lesion+. Kimmelsteil/ilson is $ery typical of diabetic nep"ropat"y. Clinical features #linical manifestation are representation of "ypoalbuminemia 5edal edema, facial puffiness, pleural effusion, ascitis 8tc. In-esti+ations "# 4rine for microalbuminuria F . Microalbuminuria is defined as '- to '-- mg3d in a 2>-" collection or '- to '-- Kg3mg creatinine in a spot collection $# 4ltra sound abdomen to rule out obstructi$e uropat"y and ot"er causes of renal failure. %# %enal functions and electrolytes. &# In$estigations to rule out ot"er complications. Mana+ement. "# )ggressi$e control of B5. 1arget B5 s"ould be belo/ 12-3<,. (rug of c"oice for diabetic nep"ropat"y /it" or /it" out "ypertension are angiotensin-con$erting en7yme *)#8+ in"ibitors e.g ramipril ,enalapril, angiotensin receptor blockers *)%Bs+ 8.g losartan,$alsaltan etc. t"eses drugs are used if )#8 in"ibitors "a$e side effects and can also be added to )#8 in"ibitors is B5 target is not reac"ed. 1"ese drugs not only reduce t"e B5 but also reduce t"e proteinuria. 1"ese drugs are contra indicated in presence of renal failure. $# 1ig"t control of sugars. )$oid using metformin if t"ere is renal failure. Incidence of renal failure, dose of insulin /ill come do/n markedly. '+ !creen for diabetic retinopat"y and ot"er complications. >+ )$oid nep"roto0ic drugs and treat 41I.

3# %enal replacement t"erapy *dialysis and renal transplantation+ is re2uired for patients /it" 8!%(.

!iabetic neuropath*
8ffects '-. of diabetics. 5at"ogenesis includes a0onal degeneration and damage to $asa ner$osum. Classification )+ !omatic 5olyneuropat"y a+ !ymmetrical, mainly sensory and distal b+ )symmetrical, mainly motor and pro0imal *including amyotrop"y+ Mononeuropat"y *including mononeuritis multiple0+ B+ Gisceral *autonomic+ #ardio$ascular, Eastrointestinal, Eenitourinary Clinical features "# !ymmetrical sensory polyneuropat"y 5arat"esia of feet and "ands *glo$e and stocking distribution+. Muscle /asting and /eakness are late features. !ensory loss and loss of (1% are t"e main features. Gibration sensation *12@H7+ is t"e first sensation to be lost. May de$elop foot ulcers*diabetic foot+ and c"arcot Doints+ $# )symmetrical diabetic motor neuropat"y #alled as diabetic amyotrop"y. #auses progressi$e /eakness and /asting of pro0imal muscles. ?eakness is asymmetrical and painful. But prognosis is good. %# Mononeuropat"y !ingle perip"eral ner$e palsy. May mimic "ensenBs disease. #ranial ner$e palsies are also common esp. 'rd and At" ner$es. 1"oracic ner$es can also be affected. #arpaltunnel syndrome can also be feature of (M. &# )utonomic neuropat"y Cardio-ascular, 5ostural "ypotension, %esting tac"ycardia Eastrointestinal - (ysp"agia, &octurnal diarr"oea or #onstipation 4enitourinar* - urinary incontinence, 8rectile dysfunction and retrograde eDaculation Others F !udomotor, $asomotor Mana+ement of neuropath* !tabili7ation and optimi7ation of glycemic control )$oidance of neuroto0ins *alco"ol, drugs+

!upplementation /it" $itamins for possible deficiencies *$itamin B12 , $itamin BA , folate+ Treatment of painful neuropaht* 1. 1ricyclic antidepressants- Amitriptyline *2,F1,- mg 56 at bedtime+ 2. !erotonin reuptake in"ibitor-Duloxetine '. )nticon$ulsants- :abapentin *'--FA-- mg 56 tid+, Carbama;epine >. 6pioid or opioid-like drugs- Tramadol *,-F2-- mg 56 bid+ ,. #apsaicin cream *-.-<,.+ -1opical analgesic applied to painful areas > times daily Treatment of Orthostatic h*potension 1+ 6ral <ludrocortisone 2+ &on p"armacologic maneu$ers may offer some benefit. )de2uate salt intake )$oidance of de"ydration and diuretics Lo/er-e0tremity support "ose Eraded super$ised e0ercise 8rectile dysfunction- ,ildena il Joot care !IA'ETIC OOT Etiolo+*. 1rauma *tri$ial+ in presence of neuropat"y and 5G( ---ulcer and infection. &europat"y or isc"aemia or bot" can cause diabetic foot. CLINICAL EATU/ES O T1E !IA'ETIC OOT Neuropath* Ischaemia S*mptoms &one &one 5araest"esiae #laudication 5ain %est pain &umbness Structural dama+e 4lcer 4lcer !epsis !epsis )bscess Eangrene 6steomyelitis (igital gangrene #"arcot Doint MANA4EMENT O !IA'ETIC OOT ULCE/S %emo$e callus skin 1reat infection )$oid /eig"t-bearing 8nsure good glycaemic control

#ontrol oedema 4ndertake angiogram to assess feasibility of $ascular reconstruction /"ere indicated. #)(, 5G( and #G) are not disscused.

SU/4E/5 AN! !IA'ETES )ll patients undergoing surgery --- catabolic stress leading to cortisol and catec"olamines and glucagon. 1"ese "ormones increase glucose le$els and increase insulin resistance and predispose t"e patient to (K) esp. if t"e sugars are uncontrolled before t"e surgery. Increase in glucose le$els also delays t"e /ound "ealing, so increase t"e post operation complications. (etails of t"e management of t"e patient before and during t"e surgery are gi$en t"e bo0.

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P/E4NANC5 AN! !IA'ETES Pre+nanc* in a diabetic patient. 4ncontrolled sugars during pregnancy can cause fetal abnormalities and increase in t"e perinatal mortality rate. Management of t"e diabetics during pregnancy is gi$en t"e bo0. 4estational diabetes !ef Hyperglycemia diagnosed first time in pregnancy. %isk factors age C2, BMI C2, 5ast "istory of gestational diabetes. family "istory of (M )ll pregnant /omen /"o are at risk s"ould be screened. 1esting for E(M s"ould be done bet/een 2>-2@/eeks.

T6o step method "# Step one. ,-gms of oral glucose *any time of t"e day+. 1"en $enous plasma sugars after one "our. &ormal ;1>-mg.: if t"e $alue is C1>-mg. proceed to step t/o. 2+ Step t6o. @"rs of fasting ,,, 1--gms of glucose orally t"en dra/ plasma $enous sample at -,1,2,' "rs. 2 or more abnormal $alues F diagnostic of E(M "# fasting F =, mg3dl $# 1"r -- 1@- mg3dl %# 2"rs --- 1,,mg3dl &# '"rs --- 1>-mg3dl Mana+ement. 5lan early deli$ery F 'A-'@/eeks due to increased risk of I4(. )$oid 6H) and control t"e sugars by insulin. Maintain t"e sugars belo/ 1-,mg3dl. 6n t"e day of deli$ery stop insulin and start glucose and insulin and K infusion and monitor sugars 2-' "rs. Maintain t"e sugars bet/een =--11- mg3dl. Jollo/-up of t"e patients /it" E(M is $ery important, as t"ey "a$e increased risk of de$eloping (M. C1EC(LIST O/ OLLO7,UP O PATIENTS 7IT1 !IA'ETES MELLITUS Urinal*sis - albumin *bot" macro- and microalbuminuria+, ketones 4l*caemic control -Elycated "aemoglobin *Hb)1c+ ,JB!, 55B!and inspection of "ome blood glucose monitoring record

 1*po+l*caemic episodes &umber of episodes and fre2uency 1ime of day /"en L"yposL e0perienced 'lood pressure F fre2uent monitoring of B5 esp in patient /it" nep"ropa"ty E*e e8amination Lo6er limbs 5erip"eral pulses ,1endon refle0es 5erception of $ibration sensation, lig"t touc" and proprioception eet #allus skin indicating pressure areas ,4lceration In-esti+ation for I1! 8#E and stress testing and ec"ocardiogram astin+ lipid profile JL5 s"ould be done once in '-A mont"s In-esti+ate for contrainfications for dru+s e.g F LJ1 for gita7ones