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Hindawi Publishing CorporationJournal o Diabetes ResearchVolume , Article ID ,pageshttp://dx.doi.org/.//

Review ArticleThe Relationship between Type 2 Diabetes Mellitusand Related Thyroid Diseases

Chaoxun Wang

Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Gongwei Road,Huinan own, Pudong, Shanghai , China

Correspondence should be addressed to Chaoxun Wang; [email protected]

Received January ; Accepted March

Academic Editor: Ake Lernmark

Copyright Chaoxun Wang. Tis is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ype diabetes mellitus (DM) has an intersecting underlying pathology with thyroid dysunction. Te literature is punctuatedwith evidence indicating a contribution o abnormalities o thyroid hormones to type DM. Te most probable mechanismleading to DM in thyroid dysunction could be attributed to perturbed genetic expression o a constellation o genes along withphysiological aberrations leading to impaired glucose utilization and disposal in muscles, overproduction o hepatic glucose output,and enhanced absorption o splanchnic glucose. Tese actors contribute to insulin resistance. Insulin resistance is also associatedwith thyroid dysunction. Hyper- and hypothyroidism have been associated with insulin resistance which has been reported to bethe major cause o impaired glucose metabolism in DM. Te state-o-art evidence suggests a pivotal role o insulin resistance

in underlining the relation between DM and thyroid dysunction. A plethora o preclinical, molecular, and clinical studies haveevidenced an undeniable role o thyroid malunctioning as a comorbid disorder o DM. It has been investigated that specicallydesigned thyroid hormone analogues can be looked upon as the potential therapeutic strategies to alleviate diabetes, obesity, andatherosclerosis. Tese molecules are in nal stages o preclinical and clinical evaluation and may pave the way to unveil a distinctclass o drugs to treat metabolic disorders.

1. Introduction

Te role o hyperthyroidism in diabetes was investigated in, by Coller and Huggins proving the association o hy-perthyroidism and worsening o diabetes. It was shown thatsurgical removal o parts o thyroid gland had an ameliorative

effect on the restoration o glucose tolerance in hyperthyroidpatients suffering rom coexisting diabetes [].

Tere is a deep underlying relation between diabetes mel-litus and thyroid dysunction []. A plethora o studies haveevidenced an array o complex intertwining biochemical, ge-netic, and hormonal malunctions mirroring this pathophys-iological association [, ]. 5 adenosine monophosphate-activatedprotein kinase (AMPK) is a central target ormodu-lation o insulin sensitivity andeedback o thyroid hormonesassociated with appetite and energy expenditure []. Hypo-thyroidism (Hashimotos thyroiditis) or thyroid over activity(Graves disease) has been investigated to be associated withdiabetes mellitus. A meta-analysis reported a requency o

% in thyroid dysunction in the patients o diabetes mellitus[]. Autoimmunity has been implicated to be the major causeo thyroid-dysunction associated diabetes mellitus [].

Unmanaged pro diabetes, both type and type , mayinduce a low state characterized by low serum total andree levels, increase in reverse (r) but near normal

serum and SH concentrations []. Te relation betweenDM andthyroid dysunction hasbeen a less explored arenawhich may behold answers to various acts o metabolic syn-drome including atherosclerosis, hypertension, and relatedcardiovascular disorders.

DM owesits pathologicalorigin to inappropriate secre-tion o insulin, due to deective islet cell unction or beta cellmass. Continuous consumption o calories-rich meals, junkood and sedentary liestyle have culminated into an epidem-ic o diabetes projected to afflict around million peopleacross the globe by []. Deective insulin secretion leadsto various metabolic aberrations in DM, spanning romhyperglycemia due to deective insulin-stimulated glucose

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Journal o Diabetes Research

uptake and upregulated hepatic glucose production, alongwith dyslipidaemia, which includes impaired homeostasis oatty acids, triglycerides, and lipoproteins [].

2. Epidemiology

Tyroid dysunction is a common endocrine disorder withvariable prevalence. Wickham survey reveals that a preva-lence o thyroid dysunction in male adults in England was.% []. According to Colorado prevalence study, .% oparticipants were ound to have elevated thyroid-stimulatinghormone (SH), while .% had a low SH. Accordingto the National Health and Nutrition Examination Survey(NHANES III Study), hypothyroidism and hyperthyroidismwere reported in .% and .% o the total participants[], respectively. Te prevalence o thyroid dysunction isadvancing with age all over the world, and requency oprevalence was higher in women than men. Te prevalenceo subclinical hypothyroidism is reported to be about to .

percent, and may be as high as percent in women olderthan years. Te prevalence o subclinical hyperthyroidismis reported to be approximately %.

Te prevalence o thyroid disorder in diabetic populationwas reported to be .% with higher prevalence (.%) inemale DM patients as compared to (.%) in male DMpatients []. Te prevalence o thyroid dysunction in DMpatients was reported to be .% in Greece and % in SaudiArabiabyAkbaretal.[]. Considerably, DMpatients weremore prone to thyroid disorders.

3. Peripheral Effects of Thyroid Hormones on

Insulin Secretion and SensitivityTyroid hormones directly control insulin secretion. In hy-pothyroidism, there is a reduction in glucose-induced insulinsecretion by beta cells, and the response o beta cells toglucose or catecholamine is increased in hyperthyroidism dueto increased beta cell mass. Moreover, insulin clearance isincreased in thyrotoxicosis [,].

.. Tyrotoxicosis. Increased glucose output rom liver is thepivotal reason or the induction o hyperinsulinaemia, induc-tion o glucose intolerance, and development o peripheralinsulin resistance []. Glucose tolerance in thyrotoxicosis is

caused by elevated hepatic glucose output along with upregu-lated glycogenolysis []. Tis phenomenon is responsible orworsening o subclinical diabetes and exaggeration o hyper-glycaemia in DM. Tyrotoxicosis may lead to ketoacidosisalso due to elevated lipolytic actions and increased hepatic oxidation [, ]. Tis phenomenon has been shown inFigure .

.. Hypothyroidism. Reduced glucose absorption rom gas-trointestinal tract accompanied by prolonged peripheral glu-cose accumulation, gluconeogenesis, diminished hepatic glu-cose output and reduced disposal o glucose are hallmarks ohypothyroidism []. In overt or subclinical hypothyroidism,

Hyperthyroidism

LipolysisGLUT 2 on liver

Lactateproduction

Hyperglycemia

Nonoxidativeglucose disposal

Free fattyacids

Hepaticglucoseoutput

F : Te relation between hyperthyroidism and hyperglycemiavia lipid metabolism oxidative stress and hepatic dysunction.

Hyperthyroidism

Reduced insulin synthesis

Decreased

Delayedgluconeogenesis

Decreasedglucose disposal

hepaticglucoseoutput

Hypoglycemia

Impaired glucoseabsorption

F : Te relation between hypothyroidism and hypoglycemiamediated by reduced insulin synthesis and impaired hepatic glucoseoutput.

insulin resistance leads to glucose-stimulated insulin secre-tion []. In subclinical hypothyroidism, diminished rate oinsulin stimulated glucose transport rate caused by perturbedexpression o glucose transporter type gene (GLU )translocation may lead to insulin resistance. Moreover, dueto reduced renal clearance o insulin in hypothyroid condi-tions, physiological requirements o insulin were diminished.Anorectic conditions in hypothyroidism may also contributeto reduced insulin in this state. An enhanced dose o insulinis required to ameliorate hypothyroidism, but the therapywarrants caution or adrenal or pituitary ailure []. Tisphenomenon has been shown inFigure .

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4. Relation between the Pathological FeaturesExhibited in Hyperthyroidism and T2DM:Role of Insulin Resistance and Other Factors

Te pathological eatures o DM include increased intesti-nal glucose absorption,reduced insulin secretion, and change

in the -cell mass []. Further, symptoms also includeincreased insulin degradation [], increased glucagon secre-tion [], increased hepatic glucose production [], en-hanced catecholamines, and insulin resistance []. Teseactors have been investigated to be an integral part o hyper-thyroidism as well []. Hence, an intersection o patholog-ical basis occurs which gives us cue to an array o physio-logical aberrations which are common in hyperthyroidismand DM. Among the above-mentioned symptomatology,insulin resistance has been the most important acet con-necting thyroid dysunction and DM. Insulin resistance isa condition which occurs in both hypothyroidism and hy-perthyroidism [].

Insulin resistance in the muscles and liver is a character-istic eature o DM. An undisturbed glucose homeostasisand intact insulin secretary response and unperturbed sensi-tivity o the tissues to insulin are essential to maintain normalblood glucose levels [].

Glucose disposal is mediated by the conjoint effect oinsulin and hyperglycemia to modulate three basic phenom-enon. Firstly, diminution o endogeneous (hepatic) glucoseproduction. Secondarily, enhanced uptake o glucose (hepaticand splanchnic). Tirdly, upregulation o glucose by periph-eral tissues (skeletal muscles). Glucose uptake into musclesis modulated by glycolysis and glycogen synthesis. Hepaticinsulin resistance is characterized by glucose overproduction

inspite o asting hyperinsulinemia, and enhanced rate ohepatic glucose output wasthe pivotal modulatoro increasedasting plasma glucose (FPG) concentration in DM sub-

jects []. In insulin resistance in the postabsorptive state,muscle glucose is upregulated but the efficiency o uptakeis reduced. In the wake o such conditions, reduced glucoseuptake into the muscles and enhanced hepatic glucose outputlead to worsening o glucose metabolism.

Te term harmonious quartet is used to address the corepathology o insulin resistance []. Deregulated glucosedisposal and metabolism in adipocytes, muscles, and liver,along with impaired insulin secretion by the pancreatic betacells, constitute the our major organ system abnormalities

which play a denitive role in the pathogenesis o DM. It isworth considering that insulin resistance has been a provencondition in hyperthyroidism as well as hypothyroidism.Insulin resistance also leads to impaired lipid metabolism ac-cording to recent ndings []. Hence, it appears that insulinresistance is the possible link between DM and thyroiddysunction.

Insulin resistance and cell unction are inversely cor-related with thyroid stimulating hormone which may beexplained by insulin-antagonistic effects o thyroid hormonesalong with anincrease in SH. Te higher serum SH usuallycorresponds to lower thyroid hormones via negative eedbackmechanism. As SH increased, thyroid hormones decreased

and insulin antagonistic effects are weakened. Tese observa-tions demonstrate that insulin imbalance is closely associatedwith thyroid dysunction and the phenomenon id mediated

via cell dysunction [].

.. Association of Insulin Resistance in Hyperthyroidism

and Subclinical Hyperthyroidism. Hyperthyroidism has beenassociated with insulin resistance which has been linkedwith elevated glucose turnover, increased intestinal glucoseabsorption, elevated hepatic glucose output, increased reeatty acid concentrations, increased asting and or postpran-dial insulin an proinsulin levels, and increased peripheralglucose transport accompanied by glucose utilization [,]. DM patients with thyroid dysunction have beenproven to be more susceptible to ketosis [] and ketogenesis[]. Insulin resistance has been shown to be associatedwith subclinical hypothyroidism, which is in turn linked toimpaired lipid balance and risk o development o metabolicsyndrome [].

... Role of Liver. In hyperthyroidism, endogenous glucoseproduction is elevated and reduces hepatic insulin sensitivityin humans [] due to glycogenesis and glycogenolysis. Terole o hypothalamus mediated sympathetic action in liverhas been proposed [] along with increased expressiono GLU transporters in liver which ultimately lead toelevation in plasma ree atty acid [,].

... Role of Muscles. Tere is marked increase in the skeletalglucose utilization in hyperthyroid state []. Increased glu-cose utilization has been reported to be mediated by insulinstimulated glucose oxidation rates []. Under such con-

ditions, reduced glyco genesis has been reported due to insu-lin stimulated nonoxidative glucose disposal, whichis accom-panied by redirection o intracellular glucose towards glycol-ysis and lactate ormation []. Te transport o lactate romperiphery to liver leads to enhanced production o glucose

via Coris cycle. Hyperthyroidism has also been associatedwith enhanced insulin sensitivity []. Increased peripheralinsulin resistance has been coupled with elevated expressiono bioactive inammatory mediators including adipokines(IL- and NF-alpha) [] which lead to insulin resistance.

... Role of Fat issues. Haluzik et al. summarized that rateo local lipolysis in the abdominal subcutaneous adipose tis-

sue was a result o modulation o norepinephrine (NE) levelsand adrenergic postreceptor signaling by thyroid hormones[]. Other studies reported that thyroid hormones are neces-sary or the mobilization o the tissue lipids especially brownadiposetissues(BAs) which are theuel or theproductionoheat []. Hypothyroidism and decreased thyroid hormonelevel are responsible or decreased thermogenesis in BA.S and lipogenesis are important actors or thermogenesismediated by thyroid hormone [].

.. Association of Insulin Resistance in Hypothyroidismand Subclinical Hypothyroidism. Insulin resistance has beenshown to be caused in hypothyroidism in various in vitro and

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preclinical studies [] where it was ound that peripheralmuscles became less responsive in hypothyroid conditions.A possible role o dysregulated metabolism o leptin hasbeen implicated or such pathology []. A direct relationbetween hypothyroidism and insulin resistance has beendemonstrated by various authors [,].

Subclinical hypothyroidism has been reported to beassociated with insulin resistance [, , ]. However,conicting ndings have also been reported by other workers[,], indicating the need o urther investigations in thisdomain.

5. Genetic Causes of T2DM and ThyroidDysfunction: The Possible Intersection

.. Effect of Tyroid Hormones on the Liver: Te Role of Genes.Various genes have been identied which are identied withgluconeogenesis, glycogen metabolism,and insulin signaling.Tese include glucose phosphate, protein kinase B (Akt),2 adrenergic receptor, inhibitory G protein (Gi), phos-phoenolpyruvate kinase (PEPCK) [], pyruvate carboxylase(PC), GLU [,], malic enzyme [], and carbohydrateresponse element binding protein (ChREBP) []. A raisedhepatic expression o GLU in hyperthyroid rats was ob-served as compared to hypothyroid rats [].

ranscription o various enzymes involved in lipid me-tabolism has been reported to increase in hyperinsulinemicor insulin-resistant mice [, ]. ranscriptional activation omalic acid has proven to be involved in atty acid synthesis[].

.. Effect of Tyroid Hormones on the Skeletal Muscle. Tevarious genes which inuence the interaction o thyroidhormone and skeletal muscles include GLU, GLU [],2adrenergic receptors [], phosphoglycerate kinase (PGK)

[], PPAR gamma coactivator- alpha (PGC- alpha) [],and mitochondrial uncoupling protein []. Amongst the

various genes identied, GLU- and UCP- have beenstudied in detail. In the skeletal muscles, GLU has beenproven to be mediated by the inuence o , and it canelevate basal and insulin mediated transport o glucose [].

Mitochondrial uncoupling protein (UCP ) is a recentlyidentied gene and has been unveiled to be associated withglucose metabolism and decreased atty acid oxidation [].It has also been reported to play a pivotalrole in the downreg-

ulated activation o Akt/PKB and 5 adenosine monophos-phate-activated protein kinase signaling [,]. Te role o has also been explored and it has been proven that it isassociated with sarcolemmal GLU-. Phosphoructokinaseand glycolytic enzymes have been associated with the -mediated GLU activity []. A number o genes have beenassociated with peripheral glucose metabolism [].

Autoimmune causes are reported to be responsible orthe genetic dysunction in the diabetic patient suffering romthyroid related disorders. However, these ndings advocatean immense clinical evidence to support association betweenDM (ype diabetes mellitus) and autoimmune thyroiddysunction (AID) [, ]. Arrays o genes involved in

metabolism o glucose are modulated by active thyroidhormone by binding to the thyroid hormone receptors.Tese receptors are derived rom R, R, R, andR. Tese are our major binding isoorms []. Ris hypothesized to regulate the metabolic effects o thyroidhormone. R and R are related with maintenance o

hypothalamic-pituitary-thyroid axis and keeping the euthy-roid state [].It has been investigated that ,,-triiodothyronine is

derived rom . It can be activated via removing an iodineatom rom the phenolic ring by the iodothyronine deiodinas-es type (D) and type (D). ype deiodinase (D) inac-tivates thyroid hormone by removing an iodine atom romthe tyrosyl ring. Te deiodinases are expressed in varioustissues, and their expression levels vary enormously duringdevelopment and are regulated by thyroid hormone status.ype deiodinase (D) is expressed in liver, while type deiod-inase (D) is expressed in adipose tissue and skeletal muscle.Tey are involved in regulation o bioavailability o andhence, the response to insulin. Elevated concentrations o are associated novel missense variant (TrAla). Tisphenomenon is closely associated with insulin resistance. It isalso associated with a surge in glucose turnover accompaniedby an upregulation o insulin-mediated glucose disposal inskeletal muscle and adipose tissue.

Tis phenomenon mediated via positive regulation oinsulin sensitive GLU- transcription [,] showed thatthere were proound genomic effects o on hepatic glucosemetabolism. R expressed in the hepatocyte and stimulationo -sensitive neurons in the hypothalamus-modulatedhepatic glucose production via sympathetic projections to theliver are mediated by circulating glucoregulatory hormones[]. Recent ndings have elucidated polymorphism o deio-dinase type (DIO) gene, TrAla, which suggest homozy-gosity or this polymorphism which in turn is responsible orenhanced risk o DM [].

A separate meta-analysis indicated that intracellular tri-iodothyronine () is responsible or aberrations in insulinsensitivity []. Ithas also been reported that polymorphism oTrAla leads to a lower activity o type deiodinase whichin turn is associated with insulin resistance. Te D gene hasa peculiar transcriptional and posttranslational regulation. Itis a potential modulator o insulin action in skeletal muscleandadipose tissue through the regulation o theGLU- genetranscription [].

Investigations using skeletal muscles in hypothyroid and

euthyroid humans have revealed a discernable inuenceon the downregulated expression o glucose transporter (GLU ) but not GLU [, ]. Glucose oxidationand glycogen synthesis are reduced in hypothyroidism [].Simultaneous increase in the insulin sensitivity occurs whenthe levels o thyroid hormone were increased. Tis phe-nomenon is governed by intracellular generation o aspolymorphismso DIO with reduced generation andalsocontributes to insulin resistance []. In hyperthyroidism,the expression o GLU is increased as compared toeuthyroid state []. In such conditions, perturbations inlipid metabolism urther link H to insulin resistance [].Tyroid hormone causes elevation in the plasma atty acid

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Increasegluconeogenesis

Lipogenesis

Decrease glycogensynthesis

Increase glucoseoutput

G-6-P,2, Gi,PC, and PEPCK

Malic enzyme,

ChREBP

Protein kinase B

Decreaseglycogensynthesis

Increase glucosetransport

Increaselipolysis

Increaseglycolysis

Increasemitochondrialfunction

GLUT 1 and 4

2-adrenoreceptor

PGK and HIF

PPAR-coactivator-

UCP-3

Liver Peripheral tissues

1

1

F : : Effect o thyroid hormones on the liver and peripheral tissues.

levels in hyperthyroid conditions but not in hypothyroid con-

ditions. Low intracellular atty acid levels are associated withhepatic insulin sensitivity via modulation o cellular insulinuptake or lipid oxidation []. Fatty acid uptake mediatedby H is a tissue-specic phenomenon and is upregulated inboth hypo, and hyperthyroidism [].

Tyrotoxicosis leads to enhanced lipid peroxidationwhereas hypothyroidism causes diminished glucose oxida-tion. LDL clearance leads to lowered cholesterol and triglyc-eride levels. H instigates upregulation o catecholamineaction leading to lipolysis on adipocytes and enhancemento circulating FA. Elevated supply o FA counteracts H-mediated elevated hepatic long-chain FA oxidative process.

Elevated circulating FA levels and availability o gluco-neogenic substrates rom peripheral reserves reciprocatesincreased gluconeogenesis in -treated animals. It has beenreported that enhances asting plasma glucose and ree FAlevels. Activation o peripheral substrates explains precipita-tion o hyperglycemia in thyrotoxicosis []. Paradoxically,hyperglycemic effect o thyrotoxicosis can be reversed byincreased blood supply to muscles providing a better supplyo substrate []. Tis phenomenon is shown inFigure .

6. Relation of Antidiabetic Therapy(Metformin) and Risk of ThyroidRelated Perturbations

Cappelli et al. evaluated the thyroid hormone prole bystudying the interaction between metormin and circulatingthyroid unction parameters in patients who were started onmetormin []. A pilot studyon diabetic hypothyroid patientrevealed baseline reduction o SH level afer months;similarly a large cohort study on diabetic patients showedsignicant all o SH level in euthyroid patients on L-substitution and subclinical hypothyroidpatientswho did notreceive L treatment, exceptin euthyroidpatientsafer yearon metormin. Tis study concluded that SH lowering effecto metormin only seen in untreated hypothyroid patientand with L- replacement therapy irrespective o thyroid

unction test. Similar ndings were reported by Vigersky

et al., Cappelli et al., and Chen et al. [].In vitro studies support the use o metormin in other

thyroid diseases other than hypothyroidism. Metormin hasinhibited the cell prolieration and growth-stimulatory effecto insulin on thyroid carcinoma cell lines. Same study showedthe stimulation o apoptosis and enhancement in the actiono chemotherapeutic agents (doxorubicin and cisplatin) bymetormin []. Other reports support growth inhibitoryeffect o metormin in mammalian cell lines mediated bymammalian target o Rapamycin (mOR) and cyclin D [].

7. Therapeutic Role of Thyroid

Hormone AnaloguesTyroid hormones have proound inuence on various physi-ological processes ranging rom metabolism o lipid, protein,and carbohydrate. Te literature is punctuated with reportsclaiming antiatherogenic and lipolytic inuences o thyroidhormones. However, their deleterious effects on bone, mus-cles, and heart are major hurdles []. Tyroid hormoneanalogues have paved the way or the development o novelstrategies in the treatment o atherosclerosis, diabetes andobesity []. Recent investigations and subsequent ndingshave provided many cues that could behold trails o complexphysiological mechanisms in the endocrine crosstalk o gly-caemic surge and thyroid dysunction [].

Development o potent thyroid hormone analogues thatselectively elude the harmul effects o thyroid hormone,and at the same time, produce desirable therapeutic effectshas been the cynosure o scientic research []. Tethrust o the research has been in designing H analogueswhich are devoid o the cardiac complications [,]. Pre-clinical investigations have demonstrated that carbohydrateresponse element-binding protein (ChREBP) is the pivotaltranscription actor modulating the stimulation o hepaticlipogenesis mediated by glucose. It is the primary target othyroid hormones in liver and white adipose tissues [].ChREBP has been reported to be regulated by Ronly andnot R in liver and white adipose tissue [].

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: Diabetic practice guidelines or thyroid screening in patients with diabetes.

Sr. no. Guidelines ype diabetes Comments

() American Tyroid Association guidelinesor detection o thyroid dysunction []

Patients with diabetes may require morerequent testing

Recommends SH rom yrs, and every yrs thereafer in all adults; high riskpersons may require more requent testsDiabetes mentioned as high-risk but doesnot distinguish between DM andDM

()American Association o ClinicalEndocrinologists, Tyroid disease clinicalPractice guidelines, []

Tyroid palpation and SH at diagnosisand at regular intervals, especially i goitreor other autoimmune disease presents

No specic recommendation or DM

()British Tyroid Association andAssociation o Clinical BiochemistryGuidelines, []

F at baseline but routine annual F isnot recommended

SH and antibodies are recommended indiabetic patients in pregnancy andpostpartum

8. Clinical Guidelines Governingthe Role of Detection of Thyroid Detectionin T2DM Patients

Various studies have been undertaken to understand the role,importance, and need o determination o thyroid dysunc-tion in the patients o DM. It has been unequivocallyapparent that testing or thyroid dysunction in DM pa-tients is necessary and should be carried out annually [].Guidelines or screening o thyroid in diabetes patients in UKand USA are presented inable .

Te American Tyroid Association guidelinesor DMpatients require requent testing or thyroid dysunction.Tey recommend testing rom years o age, and every years thereafer in adults. High-risk patients may require

more requent testing. Te American Association o ClinicalEndocrinologists, Tyroid Disease Clinical Practice Guide-lines () recommends thyroid palpation and SH indiagnosis, especially i goitre or other autoimmune diseasepresents in association with DM. Regular screening orthyroid abnormalities in all diabetic patients will allow earlytreatment o subclinical thyroid dysunction. A sensitiveserum SH assay is the screening test o choice. It has alsobeen proposed that in DM patients, a SH assay shouldbe perormed at diagnosis and then repeated at least every years.

9. Conclusion

In internal medicine, it is repeatedly proven that the asso-ciation between thyroid dysunction and diabetes mellitusis evident. Tyroid dysunction chiey comprises hypothy-roidism and hyperthyroidism although the entity belongs tothe same organ but with vast difference in pathophysiologyas well as clinical picture. Te interace between thyroidmalunction owing to diabetes is a matter o investigation.Te literature suggests that polyendocrinal multidysunctionleads to stimulation o a cascade o reactions which are actu-ally antihomeostatic in nature. For instance, hypoadrenalismas well as hypopituitarism exhibits strong linkage with hypo-thyroidism and consequently diabetes mellitus.

Recent ndings have evidenced the intricate bond be-tween subclinical hypothyroidism and diabetes mellitus thatdeceptively contribute to the major complications such as ret-inopathy and neuropathy. Cardiovascular events and micro-or macro-angiopathies are the counterreection o resur-gence o heavily disturbed lipid metabolism due to thyroiddyscrasias. It is also evident rom the existing literature thatinsulin resistance bears an indispensable role in connectingDM and thyroid dysunction. Novel molecules have shownthe path or the development o suitable thyroid hormonereceptor analogues to treat metabolic diseases. It is importantto diagnose thyroid dysunction in DM patients, andthis practice should be inculcated in clinical settings withimmediate effect to nourish urther understanding o thyroiddysunction and DM.

Conflict of Interests

Te author declares that he has no conict o interests.

Authors Contributions

Te main author contributed ully to the review.

Acknowledgment

Te author would like to thank BioQuest Solutions orproviding editorial services or this review.

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